Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Organic Chemistry  (68,947)
  • Biochemistry and Biotechnology  (16,218)
  • 1
    Keywords: Life sciences ; Biotechnology ; Organic Chemistry ; Biochemistry ; Cell Biology ; Life sciences ; Cell Biology ; Biochemistry, general ; Biotechnology ; Organic Chemistry ; Springer eBooks
    Description / Table of Contents: 1. Trends in bioprobe research -- 2. Cell proliferation and differentiation -- 3. Epigenetics -- 4. Apoptosis and autophagy -- 5. Adaptive and innate immune Systems -- 6. Bioprobes at a glance
    Abstract: This new edition provides the most advanced research using bioprobes on the chemical control of 1) cell cycle and differentiation, 2) epigenetics, 3) apoptosis and autophagy, and 4) immune response. The “bioprobe”, first proposed in the first edition, has become an indispensable tool for chemical biology and has substantially assisted in the investigation of complex biochemical processes of cells. New areas of investigation such as stem cell research, epigenetic research, and autophagy research have rapidly advanced in the past 10 years. Including these new findings, this second edition supplies up-to-date information on the biochemical tools called bioprobes. Data on each bioprobe, such as chemical structure, origin, function, and references, are presented as one item in this volume. Readers will easily find useful information and will be able to determine the appropriate bioprobes to investigate cell functions. The information on bioprobes and their use in research makes this book a valuable source for researchers in diverse fields. Not only scientists in academia but also in the pharmaceutical industries will discover the most important information about small molecules useful for drug discovery
    Pages: VIII, 384 p. 173 illus., 10 illus. in color. : online resource.
    Edition: 2nd ed. 2017.
    ISBN: 9784431565291
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    facet.materialart.
    Cham : Springer International Publishing
    Keywords: Life sciences ; Medicine ; Chemistry, Organic ; Biochemistry ; Life sciences ; Protein Science ; Biomedicine general ; Organic Chemistry ; Springer eBooks
    Description / Table of Contents: Sequences -- Structures -- Systems
    Abstract: This book describes more than 60 web-accessible computational tools for protein analysis and is totally practical, with detailed explanations on how to use these tools and interpret their results and minimal mentions to their theoretical basis (only when that is required for making a better use of them). It covers a wide range of tools for dealing with different aspects of proteins, from their sequences, to their three-dimensional structures, and the biological networks they are immersed in. The selection of tools is based on the experience of the authors that lead a protein bioinformatics facility in a large research centre, with the additional constraint that the tools should be accessible through standard web browsers without requiring the local installation of specific software, command-line tools, etc. The web tools covered include those aimed to retrieve protein information, look for similar proteins, generate pair-wise and multiple sequence alignments of protein sequences, work with protein domains and motifs, study the phylogeny of a family of proteins, retrieve, manipulate and visualize protein three-dimensional structures, predict protein structural features as well as whole three-dimensional structures, extract biological information from protein structures, summarize large protein sets, study protein interaction and metabolic networks, etc. The book is associated to a dynamic web site that will reflect changes in the web addresses of the tools, updates of these, etc. It also contains QR codes that can be scanned with any device to direct its browser to the tool web site. This monograph will be most valuable for researchers in experimental labs without specific knowledge on bioinformatics or computing
    Pages: VIII, 106 p. 40 illus. in color. : online resource.
    ISBN: 9783319127279
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: Medicine ; Neurochemistry ; Organic Chemistry ; Radiology ; Biomedicine ; Neurochemistry ; Organic Chemistry ; Imaging / Radiology ; Springer eBooks
    Abstract: This book explores the revolutionary fMRI field from basic principles to state-of-the-art research. It covers a broad spectrum of topics, including the history of fMRI's development using endogenous MR blood contrast, neurovascular coupling, pulse sequences for fMRI, quantitative fMRI, genetic imaging using fMRI, multimodal neuroimaging, brain bioenergetics and function, and molecular-level fMRI. Comprehensive and intuitively structured, this book examines the physiological basis of fMRI, the basic principles of fMRI and its applications, and the latest advances of the technology. The final chapter discusses the field's future. fMRI: From Nuclear Spins to Brain Function is an ideal resource for clinicians and researchers in the fields of neuroscience, psychology, and MRI physics. This book also: ℗ʺ℗ ℗ ℗ ℗ ℗ ℗ ℗ ℗ Explores a wide range of topics, covering the physical basics, physiological bases, a selection of various applications, and cutting-edge advances in fMRI ℗ʺ℗ ℗ ℗ ℗ ℗ ℗ ℗ ℗ Engages the reader with a first-person account of the development and history of the fMRI field by the authors ℗ʺ℗ ℗ ℗ ℗ ℗ ℗ ℗ ℗ Discusses fMRI applications in a variety of contexts, including fMRI of the visual system, auditory cortex, and sensorimotor system as well as the history of fMRI's development using endogenous MR blood contrast, neurovascular coupling, pulse sequences for fMRI, and℗ quantitative fMRI ℗
    Pages: XVIII, 929 p. 235 illus., 179 illus. in color. : online resource.
    Edition: 1st ed. 2015.
    ISBN: 9781489975911
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    facet.materialart.
    Cham : Springer International Publishing
    Keywords: Medicine ; Chemistry, Organic ; Life sciences ; Biomedicine ; Biomedicine general ; Life Sciences, general ; Organic Chemistry ; Springer eBooks
    Description / Table of Contents: Alkanes, Composition, Constitution and Configuration -- Functional Groups -- Electronic Structure of Organic Molecules -- Alkenes and Alkynes -- Substitutions on Saturated Carbon Atom -- Nucleophilic Additions -- Stereochemistry, Symmetry and Molecular Chirality -- Derivatives of Carboxylic Acids -- Electrophilic Substitutions -- Cycloadditions -- Organic Natural Products
    Abstract: This work provides an overview of the basics of organic chemistry for non-chemists. As such, this book should be very useful for university students of biology, molecular biology, ecology, medicine, agriculture, forestry, and other specialties where the knowledge of organic chemistry plays the important role but is not a core discipline. The book should also be of interest to non-professionals, and it may serve as a manual or repetitorium to high school teachers. ℗ The text is divided into eleven chapters on the basis of the systematization of fundamental organic reaction types, and classes of organic compounds. The first chapters comprise fundamental aspects of structural theory, reaction mechanisms, electronic structure, some basic spectroscopy, and properties of main groups of organic compounds. At the end of the book, the largest chapter contains the elements of the organic chemistry of natural products. Comparison of the reactions in the laboratory with the analogous molecular transformations in living cells will enable the reader to better understand the basic principles of biochemistry
    Pages: XIII, 179 p. 331 illus., 51 illus. in color. : online resource.
    ISBN: 9783319076058
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: Medicine ; Spectroscopy ; Biotechnology ; Chemistry, Organic ; Chemistry, Physical organic ; Biochemistry ; Biomedicine ; Biomedicine general ; Spectroscopy/Spectrometry ; Biotechnology ; Physical Chemistry ; Organic Chemistry ; Biochemistry, general ; Springer eBooks
    Description / Table of Contents: The basis of Nuclear Magnetic Resonance Spectroscopy -- Spectroscopic parameters in Nuclear Magnetic Resonance -- Basic NMR experiments -- Biomolecular NMR
    Abstract: This book intends to be an easy and concise introduction to the field of nuclear magnetic resonance or NMR, which has revolutionized life sciences in the last twenty years. A significant part of the progress observed in scientific areas like Chemistry, Biology or Medicine can be ascribed to the development experienced by NMR in recent times. Many of the books currently available on NMR deal with the theoretical basis and some of its main applications, but they generally demand a strong background in Physics and Mathematics for a full understanding. This book is aimed to a wide scientific audience, trying to introduce NMR by making all possible effort to remove, without losing any formality and rigor, most of the theoretical jargon that is present in other NMR books. Furthermore, illustrations are provided that show all the basic concepts using a naive vector formalism, or using a simplified approach to the particular NMR-technique described. The intention has been to show simply the foundations and main concepts of NMR, rather than seeking thorough mathematical expressions
    Pages: XII, 115 p. 36 ill. : digital.
    ISBN: 9789400769762
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    facet.materialart.
    Dordrecht : Springer
    Keywords: Medicine ; Spectroscopy ; Chemistry, Organic ; Chemistry, Physical organic ; Chemistry ; Biomedicine ; Biomedicine general ; Organic Chemistry ; Physical Chemistry ; Spectroscopy/Spectrometry ; Organometallic chemistry ; Electrochemistry ; Springer eBooks
    Description / Table of Contents: Molecular structures -- An overview of synthetic methods for preparation of nitrosoaromatic compounds -- Molecular properties and spectroscopy -- Organometallic compounds -- Bilological systems
    Abstract: This volume will present the reader with an update on the scientific research on organic chemistry of nitroso compounds that was performed in the last two decades. The overview will include the original synthetic applications of nitroso compounds, but will also cover the discovery of novel physico-chemical phenomena and their potential future uses. The properties that form the basis for this technological potential originate from the intriguing property of C-nitroso molecules to form dimers through the formation of a relatively weak nitrogen-nitrogen double bond. The equilibrium between the different monomeric and dimeric forms, which appears under controlled environmental parameters, opened new areas of research in organic chemistry.The novel paradigm presented in this volume includes insight into the original problem of organic reactivity and synthesis, but also sheds light on the solid-state reaction mechanisms. A number of fascinating photochemical, electrochemical, supramolecular, and biological properties, as well as advanced techniques in spectroscopy, now enables us to use these compounds as molecular models for studying a number of general chemical concepts.℗
    Pages: : digital.
    ISBN: 9789400763371
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Keywords: Life sciences ; Toxicology ; Chemistry, Organic ; Pharmacy ; Oceanography ; Biochemistry ; Aquatic biology ; Life sciences ; Biochemistry, general ; Organic Chemistry ; Freshwater & Marine Ecology ; Oceanography ; Pharmacology/Toxicology ; Pharmacy ; Springer eBooks
    ISBN: 9789048138340
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Keywords: Life sciences ; Chemistry, Organic ; Carbohydrates ; Biochemistry ; Proteomics ; Cytology ; Cell Membranes ; Life sciences ; Biochemistry, general ; Organic Chemistry ; Carbohydrate Chemistry ; Cell Biology ; Membrane Biology ; Proteomics ; Springer eBooks
    Pages: : digital.
    ISBN: 9781461433811
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Keywords: Medicine ; Toxicology ; Pharmaceutical technology ; Chemistry, Organic ; Chemical engineering ; Biochemistry ; Biomedicine ; Pharmacology/Toxicology ; Pharmaceutical Sciences/Technology ; Organic Chemistry ; Medicinal Chemistry ; Medical Biochemistry ; Industrial Chemistry/Chemical Engineering ; Springer eBooks
    Pages: : digital
    ISBN: 9783034801256
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    Keywords: Life sciences ; Chemistry, Organic ; Nucleic Acids ; Biochemistry ; Life sciences ; Nucleic Acid Chemistry ; Protein Science ; Organic Chemistry ; Springer eBooks
    Pages: : digital
    ISBN: 9783642169311
    Signatur Availability
    BibTip Others were also interested in ...
  • 11
    Keywords: Chemistry ; Chemistry, Organic ; Chemistry ; Organic Chemistry ; Springer eBooks
    Pages: : digital
    ISBN: 9781441972705
    Signatur Availability
    BibTip Others were also interested in ...
  • 12
    ISSN: 0887-3585
    Keywords: folding and binding ; kinetics ; pepstatin A ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The prediction of binding affinities from structure is a necessary requirement in the development of structure-based molecular design strategies. In this paper, a structural parameterization of the energetics previously developed in this laboratory has been incorporated into a molecular design algorithm aimed at identifying peptide conformations that minimize the Gibbs energy. This approach has been employed in the design of mutants of the aspartic protease inhibitor pepstatin A. The simplest design strategy involves mutation and/or chain length modification of the wild-type peptide inhibitor. The structural parameterization allows evaluation of the contribution of different amino acids to the Gibbs energy in the wild-type structure, and therefore the identification of potential targets for mutation in the original peptide. The structure of the wild-type complex is used as a template to generate families of conformational structures in which specific residues have been mutated. The most probable conformations of the mutated peptides are identified by systematically rotating around the side-chain and backbone torsional angles and calculating the Gibbs potential function of each conformation according to the structural parametrization. The accuracy of this approach has been tested by chemically synthesizing two different mutants of pepstatin A. In one mutant, the alanine at position five has been replaced by a phenylalanine, and in the second one a glutamate has been added at the carboxy terminus of pepstatin A. The thermodynamics of association of pepstatin A and the two mutants have been measured experimentally and the results compared with the predictions. The difference between experimental and predicted Gibbs energies for pepstatin A and the two mutants is 0.23 ± 0.06 kcal/mol. The excellent agreement between experimental and predicted values demonstrates that this approach can be used in the optimization of peptide ligands. Proteins 30:74-85, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 13
    ISSN: 0887-3585
    Keywords: xenon ; krypton ; hydrophobic cavity ; protein-ligand binding ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: X-ray diffraction is used to study the binding of xenon and krypton to a variety of crystallised proteins: porcine pancreatic elastase; subtilisin Carlsberg from Bacillus licheniformis; cutinase from Fusarium solani; collagenase from Hypoderma lineatum; hen egg lysozyme, the lipoamide dehydrogenase domain from the outer membrane protein P64k from Neisseria meningitidis; urate-oxidase from Aspergillus flavus, mosquitocidal δ-endotoxin CytB from Bacillus thuringiensis and the ligand-binding domain of the human nuclear retinoid-X receptor RXR-α. Under gas pressures ranging from 8 to 20 bar, xenon is able to bind to discrete sites in hydrophobic cavities, ligand and substrate binding pockets, and into the pore of channel-like structures. These xenon complexes can be used to map hydrophobic sites in proteins, or as heavy-atom derivatives in the isomorphous replacement method of structure determination. Proteins 30:61-73, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 14
    ISSN: 0887-3585
    Keywords: membrane ; protein ; structure ; prediction ; hydrophobicity ; computer ; magainin ; melittin ; 18A ; M2δ ; PGLa ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The lipid bilayer is crucial for the folding of integral membrane proteins. This article presents an empirical method to account for water-lipid interfaces in the insertion of molecules interacting with bilayers. The interactions between the molecule and the bilayer are described by restraint functions designed to mimic the membrane effect. These functions are calculated for each atom and are proportional to the accessible surface of the latter. The membrane is described as a continuous medium whose properties are varying along the axis perpendicular to the bilayer plane. The insertion is analyzed by a Monte Carlo procedure applied to the restraint functions. The method was successfully applied to small α peptides of known configurations. It provides insights of the behaviors of the peptide dynamics that cannot be obtained with statistical approaches (e.g., hydropathy analysis). Proteins 30:357-371, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 18 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 15
    ISSN: 0887-3585
    Keywords: protein modeling ; crystal structure ; conformation change ; prediction ; mechanism ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The occurrence of large domain motions associated with the mechanism of action of many proteins is well established. We present a general method of predicting domain closure applicable to proteins containing domains separated by an apparent hinge. The method attempts to allow for natural directional bias within the closing protein by repeatedly applying a weak pulling force over a short distance between pairs of atoms chosen at random in the two domains in question. Appropriate parameters governing the pulling function were determined empirically. The method was applied to the bi-lobal protein PGK and a closed-form activated ternary complex generated for Bacillus stearothermophilus PGK. This model was compared with the recently determined crystal structure of closed-form Trypanosoma brucei PGK. The model predicts the correct hinge regions, although the magnitude of movement at one hinge point was overestimated, and provides a reasonable representation of the closed-form ternary complex. Proteins 30:372-380, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 16
    ISSN: 0887-3585
    Keywords: serum amyloid A ; fluorescence ; circular dichroism ; acute phase ; denaturation ; nuclease ; amyloidosis ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: We developed a recombinant DNA system to overexpress a fusion protein between the small, minimally soluble acute phase serum protein, serum amyloid A (SAA), and the bacterial enzyme staphylococcal nuclease (SN). This fusion protein is very soluble and is immunoreactive to polyclonal anti-SAA antibodies. Tryptophan fluorescence shows smooth denaturation curves for the fusion protein in guanidinium HCl or potassium thiocyanate. Fluorescence also indicates that only a single tryptophan residue (of the four present) is accessible to iodide quenching and, presumably, is exposed on the surface of the fusion protein. Circular dichroism (CD) shows a significant signal indicating α-helix, which can be attributed to the SAA portion of the molecule; these are the first CD spectral data available for SAA. pH titration shows persistence of helix domains for the fusion protein at pH 3.0, in contrast to the denaturation of SN under the same conditions. (The entire fusion protein shows a random coil pattern below pH 3.0.) By exploiting the structural and solubility properties of SN, this fusion protein has provided the first structural data about SAA - the precursor of the amyloid deposits in secondary amyloidosis. This fusion protein should be useful for further physical and physiologic studies of SAA. Proteins 30:381-387, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 17
    ISSN: 0887-3585
    Keywords: binding free energy ; electrostatics ; group contributions ; thermodynamic cycle ; solvation ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The challenge of evaluating absolute binding free energies of protein-protein complexes is addressed using the scaled Protein Dipoles Langevin Dipoles (PDLD/S) model in combination with the Linear Response Approximation (LRA). This is done by taking the complex between Rap1A (Rap) and the p21ras binding domain of c-Raf (Raf-RBD) (Nassar et al., Nature 375:554-560, 1995) as a model system. Several formulations and different thermodynamic cycles are explored taking advantage of the LRA method and considering the protein reorganization during complex formation. The performance of different approximations is examined by comparing the calculated and observed absolute binding energies for the native complex and some of its mutants. The evaluation of the contributions of individual residues to the binding free energy, which is referred to here as group contributions is also examined. Special attention is paid to the role of the “dielectric constant,” εin which is in fact a scaling factor that represents the contributions that are treated implicitly. It is found that explicit consideration of protein relaxation is crucial for obtaining reasonable results with small values of εin, but it is also found that such a treatment of protein-protein interactions is very challenging and does not always give stable results. This indicates that more advanced explicit calculations should be based on experimentally determined structures of both the complex and the isolated proteins. Nevertheless, it is demonstrated that the qualitative trend of the effect of mutations can be reproduced by considering the effect of protein reorganization implicitly, using εin ˜25 for ionized residues and εin ˜4 for polar residues. Thus, it is concluded that an explicit treatment of solvent relaxation (which is common to current continuum models) does not provide sufficient compensation for turning off the charges of ionized residues on the interaction surface of the Raf-RBD/Rap complex. Representing the missing contribution by large εin can, of course, reproduce the observed effect of ionized residues, but now the contribution of uncharged residues will be largely underestimated. Regardless of these conceptual problems, it is established that a very simple nonrelaxed approach, where the relaxation of both the protein and the solvent are considered implicitly, can provide an effective qualitative way for evaluating group contributions, using large and small values for εin of ionized and neutral residues, respectively. As much as the actual system studied is concerned we find that more residues than generally assumed play a role in Raf-RBD/Rap interaction. This includes residues that are not located at the protein-protein interaction surface. These residues contribute to the binding energy through direct charge-charge interaction without leading to drastic structural changes. The overall contribution of the surface residues is quite significant since Raf and Rap are positively and negatively charged, respectively, and their charges are distributed along the interaction site between the two proteins. Proteins 30:407-423, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 18
    ISSN: 0887-3585
    Keywords: protease II ; intrinsic fluorescence ; ionic strength ; heat denaturation ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Oligopeptidase B is a member of a new serine peptidase family, unrelated to the trypsin and subtilisin families. It is a potential processing enzyme of prokaryotes, being very specific for the basic amino acid pairs of polypeptides. An understanding of the kinetics of the enzyme requires the examination of its conformational stability under a variety of conditions. To this end, the enzyme was cloned from Escherichia coli HB101 by the PCR method, expressed with high yield in E. coli XL1-Blue, and purified essentially in two chromatographic steps. The denatured enzyme failed to refold, which precluded the calculation of free energy of stability, ΔG0. Therefore, the unfolding rates were measured to probe the stability against urea, pH, and heat. Denaturation processes were monitored by intrinsic fluorescence, circular dichroism, and activity measurements. A static method, intrinsic fluorescence vs. pH, was indicative of significant changes in the tertiary structure of the enzyme pH < 6 and pH > 8.5. The more sensitive dynamic methods, unfolding rates in urea and inactivation rates at high temperature, revealed increased flexibility in the protein structure between pH 6 and pH 7, where the static method did not show significant changes. Inactivation of the enzyme in the acidic pH range correlated with the results obtained with the static rather than with the dynamic method. Acid denaturation at pH 3 was markedly retarded by 1 M NaCl. Against heat inactivation the enzyme was also considerably protected in the presence of salt, and the higher enthalpy and entropy of activation suggested the importance of hydration in the stabilization. The kinetics of unfolding followed single-exponential decay under strongly denaturing conditions (high urea concentration or high temperature), but deviated from the apparently two-state mechanism at low urea concentrations and at slightly acidic pH. The results indicate that under harsher denaturing conditions there is a single rate-limiting step in unfolding, whereas under milder conditions partly unfolded intermediates are populated. Proteins 30:424-434, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 19
    ISSN: 0887-3585
    Keywords: molecular dynamics ; free energy perturbation ; thermodynamics integration ; spherical solvent boundary potential ; cell multipole method ; Nosé-Hoover equation ; component analysis ; chymotrypsin inhibitor 2 ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: We developed a software package for improved free energy calculation, in which spherical solvent boundary potential, cell multipole method, and Nosé-Hoover equation are employed. The performance of the developed software package is demonstrated in the case of valine to alanine mutation of the 57th residue in chymotrypsin inhibitor 2. By using this package, we obtained results quantitatively comparable to experimental results. By the free energy component analysis, it is shown that leucine 51, arginine 65, arginine 67, and phenylalanine 69 residues contribute significantly to the total free energy shift, ΔΔG. Among them, contribution from the hydrophilic arginine 67 residue, which is in close contact with the mutation site, is the largest. Structure around the mutation site is largely changed by the mutation. The structure change is caused mainly by two effects, hydrophobic interaction and short-range interaction along the sequence. Effects of Nosé-Hoover algorithm and Kirkwood reaction field are also discussed. Proteins 30:388-400, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 20
    ISSN: 0887-3585
    Keywords: protein stability ; cold shock domain ; nucleic acid binding ; hydrophobic effect ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: In the cold-shock protein CspB from Bacillus subtilis three exposed Phe residues (F15, F17, and F27) are essential for its function in binding to single-stranded nucleic acids. Usually, the hydrophobic Phe side chains are buried in folded proteins. We asked here whether the exposition of the essential Phe residues could be a cause for the very low conformational stability of CspB. Urea-induced and heat-induced equilibrium unfolding transitions were measured for three mutants of CspB, where Phe 15, Phe 17, and Phe 27 were individually replaced by alanine. Unexpectedly, all three mutations strongly destabilized CspB. The aromatic side chains of Phe 15, Phe 17, and Phe 27 in the active site are thus important for both binding to nucleic acids and conformational stability. There is no compromise between function and stability in the active site. Model calculations indicate that, although they are partially exposed to solvent, all three Phe residues nevertheless lose accessible surface upon folding, and this should favor the native state. A different result is obtained with the F38A variant. Phe 38 is hyperexposed in native CspB, and its substitution by Ala is in fact stabilizing. Proteins 30:401-406, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 21
    ISSN: 0887-3585
    Keywords: cytochrome c ; thermal unfolding ; proteolysis ; proteinase K ; thermolysin ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Recent hydrogen exchange experiments on native cytochrome c implicate a sequential unfolding pathway in contrast to a simple two-state process. We have studied the heat-induced unfolding of this protein by using spectroscopic measurements to detect changes in conformation and proteolytic enzyme digestion to identify regions of the protein that are labile. Several spectroscopic profiles were monitored: CD at 222 nm, a measurement of secondary structure change in the protein, the absorbance at 280 nm, involving the local environment of Trp 59, and absorbance at 420 nm, the Soret band of the heme. The apparent Tm values for these probes differ, consistent with an unfolding pathway containing intermediates. The limited digestion by proteinase K is consistent with population of an intermediate state in unfolding. We find a single strong region of cleavage at low temperature with retention of structure in each fragment. Proteins 30:435-441, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 22
    ISSN: 0887-3585
    Keywords: pleckstrin homology domain ; DNA sequence homology ; DNA sequence patterns ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Pleckstrin homology (PH) domains have been proven to bind phosphoinositides (PI) and inositolphosphates (IP). On the other hand, a binding of PH domains to proteins is still a matter of debate. The goal of this work was to identify potential PH domain protein target sites and to build a model for PH domain-protein binding. A candidate sequence, called HIKE, was identified by sequence homology analysis of the proteins that are considered the strongest PH binding candidates, i.e., Gβ, PKC, and Akt. HIKE contains a PI binding sequence and fulfills several criteria for a potential PH-binding site, i.e., it is present in other PH-binding candidates, lies in regulatory regions independently predicted to bind PH domains, and is conserved in 3-D structure among different molecules. These findings and the similarities with the mode of binding of PTB and PDZ domains suggest a β strand-β strand coordination model for PH-protein binding. The HIKE model predicts that membrane anchoring of PH domains and their targets could be a critical step in their interaction, which would consistently explain why PH-protein binding has only been detected in the presence of PI. Proteins 31:1-9, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 23
    ISSN: 0887-3585
    Keywords: protein design ; lattice model ; protein stability ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A structure-based, sequence-design procedure is proposed in which one considers a set of decoy structures that compete significantly with the target structure in being low energy conformations. The decoy structures are chosen to have strong overlaps in contacts with the putative native state. The procedure allows the design of sequences with large and small stability gaps in a random-bond heteropolymer model in both two and three dimensions by an appropriate assignment of the contact energies to both the native and nonnative contacts. The design procedure is also successfully applied to the two-dimensional HP model. Proteins 31:10-20, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 24
    ISSN: 0887-3585
    Keywords: subtilisin BPN′ ; proenzyme ; protein folding ; protein crystallography ; thermal stability ; calcium binding ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The three-dimensional structure of a subtilisin BPN′ construct that was produced and folded without its prodomain shows the tertiary structure is nearly identical to the wild-type enzyme and not a folding intermediate. The subtilisin BPN′ variant, Sbt70, was cloned and expressed in Escherichia coli without the prodomain, the 77-residue N-terminal domain that catalyzes the folding of the enzyme into its native tertiary structure. Sbt70 has the high-affinity calcium-binding loop, residues 75 to 83, deleted. Such calcium-independent forms of subtilisin BPN′ refold independently while retaining high levels of activity [Bryan et al., Biochemistry, 31:4937-4945, 1992]. Sbt70 has, in addition, seven stabilizing mutations, K43N, M50F, A73L, Q206V, Y217K, N218S, Q271E, and the active site serine has been replaced with alanine to prevent autolysis. The purified Sbt70 folded spontaneously without the prodomain and crystallized at room temperature. Crystals of Sbt70 belong to space group P212121 with unit cell parameters a = 53.5 Å, b = 60.3 Å, and c = 83.4 Å. Comparison of the refined structure with other high-resolution structures of subtilisin BPN′ establishes that the conformation of Sbt70 is essentially the same as that previously determined for other calcium-independent forms and that of other wild-type subtilisin BPN′ structures, all folded in the presence of the prodomain. These findings confirm the results of previous solution studies that showed subtilisin BPN′ can be refolded into a native conformation without the presence of the prodomain [Bryan et al., Biochemistry 31:4937-4945, 1992]. The structure analysis also provides the first descriptions of four stabilizing mutations, K43N, A73L, Q206V, and Q271E, and provides details of the interaction between the enzyme and the Ala-Leu-Ala-Leu tetrapeptide found in the active-site cleft. Proteins 31:21-32, 1998. Published 1998 Wiley-Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 25
    ISSN: 0887-3585
    Keywords: quantum chemistry ; molecular mechanics ; inhibitor ; metalloenzyme complexes ; selectivity ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: We investigated the binding properties of the metalloprotease inhibitors hydroxamate, methanethiolate, and methylphosphoramidate to a model coordination site occurring in several Zn2+ metalloproteases, including thermolysin. This was carried out using both the SIBFA (sum of interactions between fragments ab initio-computed) molecular mechanics and the SCF/MP2 procedures for the purpose of evaluating SIBFA as a metalloenzyme modeling tool. The energy-minimized structures were closely similar to the X-ray crystallographic structures of related thermolysin-inhibitor complexes. We found that selectivity between alternative geometries and between inhibitors usually stemmed from multiple interaction components included in SIBFA. The binding strength sequence is hydroxamate > methanethiolate ≥ methylphosphoramidate from multiple interaction components included in SIBFA. The trends in interaction energy components, rankings, and preferences for mono- or bidentate binding were consistent in both computational procedures. We also compared the Zn2+ vs. Mg2+ selectivities in several other polycoordinated sites having various “hard” and “soft” qualities. This included a hexahydrate, a model representing Mg2+/Ca2+ binding sites, a chlorophyll-like structure, and a zinc finger model. The latter three favor Zn2+ over Mg2+ by a greater degree than the hydrated state, but the selectivity varies widely according to the ligand “softness.” SIBFA was able to match the ab initio binding energies by <2%, with the SIBFA terms representing dispersion and charge-transfer contributing the most to Zn2+/Mg2+ selectivity. These results showed this procedure to be a very capable modeling tool for metalloenzyme problems, in this case giving valuable information about details and limitations of “hard” and “soft” selectivity trends. Proteins 31:42-60, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 26
    ISSN: 0887-3585
    Keywords: ricin structure ; inhibitor design ; energy minimization ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Ricin A-chain is an N-glucosidase that attacks ribosomal RNA at a highly conserved adenine residue. Our recent crystallographic studies show that not only adenine and formycin, but also pterin-based rings can bind in the active site of ricin. For a better understanding of the means by which ricin recognizes adenine rings, the geometries and interaction energies were calculated for a number of complexes between ricin and tautomeric modifications of formycin, adenine, pterin, and guanine. These were studied by molecular mechanics, semi-empirical quantum mechanics, and ab initio quantum mechanical methods. The calculations indicate that the formycin ring binds better than adenine and pterin better than formycin, a result that is consistent with the crystallographic data. A tautomer of pterin that is not in the low energy form in either the gas phase or in aqueous solution has the best interaction with the enzyme. The net interaction energy, defined as the interaction energy calculated in vacuo between the receptor and an inhibitor minus the solvation energy of the inhibitor, provides a good prediction of the ability of the inhibitor to bind to the receptor. The results from experimental and molecular modeling work suggest that the ricin binding site is not flexible and may only recognize a limited range of adenine-like rings. Proteins 31:33-41, 1998. Published 1998 Wiley-Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 27
    ISSN: 0887-3585
    Keywords: mutagenesis ; protein stability ; salt bridge ; protein folding ; malic enzyme ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A double mutant (R9E/M17K) of pigeon liver malic enzyme with glutamate and lysine replaced for arginine and methionine at positions 9 and 17, respectively, was found to be much more stable in urea and thermal denaturation, but was enzymatically less active than the wild-type enzyme (WT). Unfolding of the enzyme by urea produced a large red shifting of the protein fluorescence maximum from 320 to 360 nm, which was completely reversible upon dilution. Analysis of the denaturation curves monitored by enzyme activity lost suggested that a putative intermediate was involved in the denaturation process. The half unfolding urea concentration, measured by fluorescence spectral changes, increased from 2.24 M for WT to 3.13 M for R9E/M17K. The melting temperature increased by approximately 10°C for R9E/M17K compared with that for WT. Kinetic analysis of the thermal inactivation at 58°C also conformed to a three-state model with the rate constant for the intermediate state of R9E/M17K (k2 = 0.03 min-1) being much smaller than the WT value (k2= 2.39 min-1). Results obtained from single mutants indicated that the decreasing enzyme activity of R9E/M17K was exclusively due to R9 mutation, which increased the KmMn and KmMal by at least one order of magnitude compared with WT. Consequently, a decrease occurred in the specificity constant [kcat/(KmMnKmNADPKmMal)] for the R9 mutants at least four orders of magnitude smaller than the WT. M17K has similar properties to the WT, while R9E is more labile than the WT enzyme. The above results indicate that the extra stability gained by the double mutant possibly occurs through the introduction of an extra ion-pair between E9 and K17, which freezes the double mutant in the putative intermediate state. Examination of the N-terminal amino acid sequence of pigeon liver malic enzyme reveals that position 15 is also a lysine residue. Since the R9E mutant, which has an extra Glu9-Lys15 ion-pair, is less stable than the WT, we conclude that the contribution to malic enzyme stability is specific for the Glu9-Lys17 ion-pair. Proteins 31:61-73, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 28
    ISSN: 0887-3585
    Keywords: α domains ; β domains ; α/β domains ; α+β domains ; resubstitution ; jackknife ; SCOP database ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Can the coupling effect among different amino acid components be used to improve the prediction of protein structural classes? The answer is yes according to the study by Chou and Zhang (Crit. Rev. Biochem. Mol. Biol. 30:275-349, 1995), but a completely opposite conclusion was drawn by Eisenhaber et al. when using a different dataset constructed by themselves (Proteins 25:169-179, 1996). To resolve such a perplexing problem, predictions were performed by various approaches for the datasets from an objective database, the SCOP database (Murzin, Brenner, Hubbard, and Chothia. J. Mol. Biol. 247:536-540, 1995). According to SCOP, the classification of structural classes for protein domains is based on the evolutionary relationship and on the principles that govern the 3D structure of proteins, and hence is more natural and reliable. The results from both resubstitution tests and jackknife tests indicate that the overall rates of correct prediction by the algorithm incorporated with the coupling effect among different amino acid components are significantly higher than those by the algorithms without using such an effect. It is elucidated through an analysis that the main reasons for Eisenhaber et al. to have reached an opposite conclusion are the result of (1) misusing the component-coupled algorithm, and (2) using a conceptually incorrect rule to classify protein structural classes. The formulation and analysis presented in this article are conducive to clarify these problems, helping correctly to apply the prediction algorithm and interpret the results. Proteins 31:97-103, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 4 Tab.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 29
    ISSN: 0887-3585
    Keywords: molecular dynamics ; X-ray crystallography ; essential dynamics ; lysozyme ; hinge bending ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A comparison of a series of extended molecular dynamics (MD) simulations of bacteriophage T4 lysozyme in solvent with X-ray data is presented. Essential dynamics analyses were used to derive collective fluctuations from both the simulated trajectories and a distribution of crystallographic conformations. In both cases the main collective fluctuations describe domain motions. The protein consists of an N- and C-terminal domain connected by a long helix. The analysis of the distribution of crystallographic conformations reveals that the N-terminal helix rotates together with either of these two domains. The main domain fluctuation describes a closure mode of the two domains in which the N-terminal helix rotates concertedly with the C-terminal domain, while the domain fluctuation with second largest amplitude corresponds to a twisting mode of the two domains, with the N-terminal helix rotating concertedly with the N-terminal domain. For the closure mode, the difference in hinge-bending angle between the most open and most closed X-ray structure along this mode is 49 degrees. In the MD simulation that shows the largest fluctuation along this mode, a rotation of 45 degrees was observed. Although the twisting mode has much less freedom than the closure mode in the distribution of crystallographic conformations, experimental results suggest that it might be functionally important. Interestingly, the twisting mode is sampled more extensively in all MD simulations than it is in the distribution of X-ray conformations. Proteins 31:116-127, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 30
    ISSN: 0887-3585
    Keywords: acid denatured state ; ANS fluorescence ; Arrhenius plot ; kinetics ; molten globule intermediate ; TFE denatured state ; protein folding ; human stefin B ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: It has been shown that human stefin B exhibits molten globule intermediates when denatured by acid or GuHCl. In the presence of TFE, it transforms into a highly helical state. In our first study on its folding mechanism (Žerovnik et al., Proteins 32:296-303), the kinetics measured by circular dichroism (CD) and fluorescence were correlated. In the present work the kinetics of folding were monitored by tyrosine fluorescence, ANS fluorescence, and, for certain reactions, far ultraviolet (UV) CD. The folding was started from the unfolded state in 3.45 M GuHCl, the acid denatured state at pH 1.8 ± 0.2, an acid molten globule intermediate I1 (pH 3.3 ± 0.1, low salt), a more structured acid molten globule intermediate I2 (pH 3.3 ± 0.1, 0.42 M NaCl), and the TFE state (pH 3.3 ± 0.1, 42% TFE). It has been found that all denatured states, including GuHCl, TFE, acid denatured and acid molten globule intermediate I1, fold with the same kinetics, provided that the final conditions are identical. This does not apply to the second acid molten globule intermediate I2, which demonstrates a higher rate of folding by a factor of 270. Different energy of activation and pH dependence were found for folding from states I1 or I2. Proteins 32:304-313, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 31
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    ISSN: 0887-3585
    Keywords: molecular evolution ; protein evolution ; mutation matrices ; Metropolis kinetics ; Boltzmann statistics ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: New computational models of natural site mutations are developed that account for the different selective pressures acting on different locations in the protein. The number of adjustable parameters is greatly reduced by basing the models on the underlying physical-chemical properties of the amino acids. This allows us to use our method on small data sets built of specific protein types. We demonstrate that with this approach we can represent the evolutionary patterns in HIV envelope proteins far better than with more traditional methods. Proteins 32:289-295, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 32
    ISSN: 0887-3585
    Keywords: antivirals ; Zovirax ; drug target ; drug binding ; enzyme structure ; intermolecular interactions ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Antiherpes therapies are principally targeted at viral thymidine kinases and utilize nucleoside analogs, the triphosphates of which are inhibitors of viral DNA polymerase or result in toxic effects when incorporated into DNA. The most frequently used drug, aciclovir (Zovirax), is a relatively poor substrate for thymidine kinase and high-resolution structural information on drugs and other molecules binding to the target is therefore important for the design of novel and more potent chemotherapy, both in antiherpes treatment and in gene therapy systems where thymidine kinase is expressed. Here, we report for the first time the binary complexes of HSV-1 thymidine kinase (TK) with the drug molecules aciclovir and penciclovir, determined by X-ray crystallography at 2.37 Å resolution. Moreover, from new data at 2.14 Å resolution, the refined structure of the complex of TK with its substrate deoxythymidine (R = 0.209 for 96% of all data) now reveals much detail concerning substrate and solvent interactions with the enzyme. Structures of the complexes of TK with four halogen-containing substrate analogs have also been solved, to resolutions better than 2.4 Å. The various TK inhibitors broadly fall into three groups which together probe the space of the enzyme active site in a manner that no one molecule does alone, so giving a composite picture of active site interactions that can be exploited in the design of novel compounds. Proteins 32:350-361, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 33
    ISSN: 0887-3585
    Keywords: molecular dynamics simulations ; mutagenesis ; aminoacyl-tRNA synthetase ; ATP ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Histidyl-tRNA synthetase (HisRS) differs from other class II aminoacyl-tRNA synthetases (aaRS) in that it harbors an arginine at a position where the others bind a catalytic Mg2+ ion. In computer experiments, four mutants of HisRS from Escherichia coli were engineered by removing the arginine and introducing a Mg2+ ion and residues from seryl-tRNA synthetase (SerRS) that are involved in Mg2+ binding. The mutants recreate an active site carboxylate pair conserved in other class II aaRSs, in two possible orders: Glu-Asp or Asp-Glu, replacing Glu-Thr in native HisRS. The mutants were simulated by molecular dynamics in complex with histidyl-adenylate. As controls, the native HisRS was simulated in complexes with histidine, histidyl-adenylate, and histidinol. The native structures sampled were in good agreement with experimental structures and biochemical data. The two mutants with the Glu-Asp sequence showed significant differences in active site structure and Mg2+ coordination from SerRS. The others were more similar to SerRS, and one of them was analyzed further through simulations in complex with histidine, and His+ATP. The latter complex sampled two Mg2+ positions, depending on the conformation of a loop anchoring the second carboxylate. The lowest energy conformation led to an active site geometry very similar to SerRS, with the principal Mg2+ bridging the α- and β-phosphates, the first carboxylate (Asp) coordinating the ion through a water molecule, and the second (Glu) coordinating it directly. This mutant is expected to be catalytically active and suggests a basis for the previously unexplained conservation of the active site Asp-Glu pair in class II aaRSs other than HisRS. Proteins 32:362-380, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 34
    ISSN: 0887-3585
    Keywords: P1 nuclease ; X-ray crystallography ; substrate recognition ; catalytic mechanism ; thiophosphorylated oligonucleotides ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The reaction mechanism of nuclease P1 from Penicillium citrinum has been investigated using single-stranded dithiophosphorylated di-, tetra-, and hexanucleotides as substrate analogs. The complexes crystallize in tetragonal and orthorhombic space groups and have been solved by molecular replacement. The high resolution structures give a clear picture of base recognition by P1 nuclease at its two nucleotide-binding sites, especially the 1.8 Å structure of a P1-tetranucleotide complex which can be considered a P1-product complex. The observed binding modes are in agreement with a catalytic mechanism where the two closely spaced zinc ions activate the attacking water while the third, more exposed zinc ion stabilizes the leaving 03' oxyanion. Stacking as well as hydrogen bonding interactions with the base 5' to the cleaved phosphodiester bond are important elements of substrate binding and recognition. Modelling of a productive P1-substrate complex based on the solved structures suggests steric hindrance as the likely reason for the resistance of Rp-phosphorothioates and phosphorodithioates. Differences with the highly homologous nuclease S1 from Aspargillus oryzae are discussed. Proteins 32:414-424, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 35
    ISSN: 0887-3585
    Keywords: theory of protein folding ; folding funnel ; folding thermodynamics ; folding kinetics ; conformation space ; sequence/structure compatibility ; thermal denaturation ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: It is hard to construct theories for the folding of globular proteins because they are large and complicated molecules having enormous numbers of nonnative conformations and having native states that are complicated to describe. Statistical mechanical theories of protein folding are constructed around major simplifying assumptions about the energy as a function of conformation and/or simplifications of the representation of the polypeptide chain, such as one point per residue on a cubic lattice. It is not clear how the results of these theories are affected by their various simplifications. Here we take a very different simplification approach where the chain is accurately represented and the energy of each conformation is calculated by a not unreasonable empirical function. However, the set of amino acid sequences and allowed conformations is so restricted that it becomes computationally feasible to examine them all. Hence we are able to calculate melting curves for thermal denaturation as well as the detailed kinetic pathway of refolding. Such calculations are based on a novel representation of the conformations as points in an abstract 12-dimensional Euclidean conformation space. Fast folding sequences have relatively high melting temperatures, native structures with relatively low energies, small kinetic barriers between local minima, and relatively many conformations in the global energy minimum's watershed. In contrast to other folding theories, these models show no necessary relationship between fast folding and an overall funnel shape to the energy surface, or a large energy gap between the native and the lowest nonnative structure, or the depth of the native energy minimum compared to the roughness of the energy landscape. Proteins 32:425-437, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 14 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 36
    ISSN: 0887-3585
    Keywords: protein inhibitors ; serine proteinases ; protein loop ; canonical conformation ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Canonical loops of protein inhibitors of serine proteinases occur in proteins having completely different folds. In this article, conformations of the loops have been analyzed for inhibitors belonging to 10 structurally different families. Using deviation in Cα-Cα distances as a criterion for loop similarity, we found that the P3-P3′ segment defines most properly the length of the loop. When conformational differences among loops of individual inhibitors were compared using root mean square deviation (rmsd) in atomic coordinates for all main chain atoms (Δr method) and rmsd operating in main chain torsion angles (Δt method), differences of up to 2.1 Å and 72.3°, respectively, were observed. Such large values indicate significant conformational differences among individual loops. Nevertheless, the overall geometry of the inhibitor-proteinase interaction is very well preserved, as judged from the similarity of Cα-Cα distances between Cα of catalytic Ser and Cα of P3-P3′ residues in various enzyme-inhibitor complexes. The mode of interaction is very well preserved both in the chymotrypsin and subtilisin families, as distances calculated for subtilisin-inhibitor complexes are almost always within the range of those for chymotrypsin-inhibitor complexes. Complex formation leads to conformational changes of up to 160° for χ1 angle. Side chains of residue P1 and P2′ adopt in different complexes a similar orientation (χ1 angle = -60° and -180°, respectively). To check whether the canonical conformation can be found among non-proteinase-inhibitor Brookhaven Protein Data Bank structures, two selection criteria - the allowed main chain dihedral angles and Cα-Cα distances for the P3-P3′ segment - were applied to all these structures. This procedure detected 132 unique hexapeptide segments in 121 structurally and functionally unrelated proteins. Partial preferences for certain amino acids occurring at particular positions in these hexapeptides could be noted. Further restriction of this set to hexapeptides with a highly exposed P1 residue side chain resulted in 40 segments. The possibility of complexes formation between these segments and serine proteinases was ruled out in molecular modeling due to steric clashes. Several structural features that determine the canonical conformation of the loop both in inhibitors and in other proteins can be distinguished. They include main chain hydrogen bonds both within the P3-P3′ segment and with the scaffold region, P3-P4 and P3′-P4′ hydrophobic interactions, and finally either hydrophobic or polar interactions involving the P1′ residue. Proteins 32:459-474, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 37
    ISSN: 0887-3585
    Keywords: megakaryocyte growth and development factor ; thrombopoietin ; cytokine ; equilibrium denaturation ; conformation ; protein folding ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The effect of pH and urea on the conformation of recombinant human megakaryocyte growth and development factor (rHuMGDF) was determined by circular dichroism, intrinsic fluorescence spectroscopy, and equilibrium ultracentrifugation. The conformation of rHuMGDF was dependent on pH and urea concentration. Multiple folding forms were evidenced by multiple pH-induced transitions and urea-induced equilibrium transitions that deviated from a simple two-state process. In neutral to alkaline pH, rHuMGDF exists as a monomer, but an acid-induced conformational state self-associates to form a soluble aggregate. A folding intermediate(s) was observed with a more stable secondary structure than tertiary structure and was dependent on the pH of the urea-induced denaturation. The differences in the stabilities of the folding states were most distinct in the pH range of 4.5 to 6.5. The presence of intermediates in the folding pathway of rHuMGDF are similar to findings of previous studies of related growth factors that share a common three-dimensional structure. Proteins 32:495-503, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 38
    ISSN: 0887-3585
    Keywords: sugar ; acetamido group ; mimicry ; inhibition ; lysozyme ; CDR loop ; VHH ; heavy-chain immunoglobulin ; solvent accessible surface area ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Whereas antibodies have demonstrated the ability to mimic various compounds, classic heavy/light-chain antibodies may be limited in their applications. First, they tend not to bind enzyme active site clefts. Second, their size and complexity present problems in identifying key elements for binding and in using these elements to produce clinically valuable compounds. We have previously shown how cAb-Lys3, a single variable domain fragment derived from a lysozyme-specific camel antibody naturally lacking light chains, overcomes the first limitation to become the first antibody structure observed penetrating an enzyme active site. We now demonstrate how cAb-Lys3 mimics the oligosaccharide substrate functionally (inhibition constant for lysozyme, 50 nM) and structurally (lysozyme buried surface areas, hydrogen bond partners, and hydrophobic contacts are similar to those seen in sugar-complexed structures). Most striking is the mimicry by the antibody complementary determining region 3 (CDR3) loop, especially Ala104, which mimics the subsite C sugar 2-acetamido group; this group has previously been identified as a key feature in binding lysozyme. Comparative simplicity, high affinity and specificity, potential to reach and interact with active sites, and ability to mimic substrate suggest that camel heavy-chain antibodies present advantages over classic antibodies in the design, production, and application of clinically valuable compounds. Proteins 32:515-522, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 39
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Recently, James Bowie addressed the question of how to normalize correctly the distribution of observed helix-helix packing angles in proteins (Bowie, Nature Struct. Biol. 4:915-917, 1997). A hitherto unrealized yet significant bias toward crossed packing angles was revealed. However, the derived random reference distribution of packing angles requires that helices have to be assumed as infinite in length. Here, we complement Bowie's analysis by consideration of the more realistic case where helices are of finite length. As a result, the statistical bias toward near perpendicular packings appears to be even stronger. Proteins 33:457-459, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 40
    ISSN: 0887-3585
    Keywords: MS/MS electrospray mass spectrometry ; CD ; human immunodeficiency virus (HIV) ; glycoprotein 41,000 (gp41) ; N-terminal domain ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The N-terminal domain of human immunodeficiency virus (HIV)-1 glycoprotein 41,000 (FP; residues 1-23; NH2-AVGIGALFLGFLGAAGSTMGARS-CONH2) is involved in the fusion and cytolytic processes underlying viral-cell infection. Here, we use circular dichroism (CD) spectroscopy, along with electrospray ionization (ESI) mass spectrometry and tandem (MS/MS) mass spectrometry during the course of hydrogen/deuterium exchange, to probe the local conformations of this synthetic peptide in two membrane mimics. Since amino acids that participate in defined secondary structure (i.e., α-helix or β-sheet) exchange amido hydrogens more slowly than residues in random structures, deuterium exchange was combined with CD spectroscopy to map conformations to specific residues. For FP suspended in the highly structure-promoting solvent hexafluoroisopropanol (HFIP), CD spectra indicated high α-helix and disordered structures, whereas ESI and MS/MS mass spectrometry indicated that residues 5-15 were α-helical and 16-23 were disordered. For FP suspended in the less structure-promoting solvent trifluoroethanol (TFE), CD spectra showed lower α-helix, with ESI and MS/MS mass spectrometry indicating that only residues 9-15 participated in the α-helix. These results compare favorably with previous two-dimensional nuclear magnetic resonance studies on the same peptide. Proteins Suppl. 2:38-49, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 41
    ISSN: 0887-3585
    Keywords: MALDI mass spectrometric peptide mapping ; membrane proteins ; in situ gel digestion ; porin ; permeability transition ; noncovalent complexes ; protein interactions ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Mass spectrometric peptide mapping, particularly by matrix-assisted laser desorption-ionization (MALDI-MS), has recently been shown to be an efficient tool for the primary structure characterization of proteins. In combination with in situ proteolytic digestion of proteins separated by one- and two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), mass spectrometric peptide mapping permits identification of proteins from complex mixtures such as cell lysates. In this study we have investigated several ion channel membrane proteins (porins) and their supramolecular assembly in mitochondrial membranes by peptide mapping in solution and upon digestion in the gel matrix. Porins are integral membrane proteins serving as nonspecific diffusion pores or as specific systems for the transport of substrates through bacterial and mitochondrial membranes. The well-characterized porin from Rhodobacter capsulatus (R.c.-porin) has been found to be a native trimeric complex by the crystal structure and was used as a model system in this study. R.c.-porin was characterized by MALDI-MS peptide mapping in solution, and by direct in situ-gel digestion of the trimer. Furthermore, in this study we demonstrate the direct identification of the noncovalent complex between a mitochondrial porin and the adenine nucleotide translocator from rat liver, by MALDI-MS determination of the specific peptides due to both protein sequences in the SDS-PAGE gel band. The combination of native gel electrophoresis and mass spectrometric peptide mapping of the specific gel bands should be developed as a powerful tool for the molecular identification of protein interactions. Proteins Suppl. 2:63-73, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 42
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 492-498 
    ISSN: 0899-0042
    Keywords: racemate ; enantiomer ; HPLC ; chiral stationary phase ; benzoylcellulose ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The advantages that can be gained from derivatization of various racemic aliphatic and aromatic alcohols prior to enantiomeric chromatographic separation have been systematically investigated for a series of benzoate derivatives. Three cellulose-based CSPs available in the pure polymeric form - tribenzoyl cellulose (TBC), meta-methylbenzoyl cellulose (MMBC), and para-methylbenzoyl cellulose (PMBC) - were selected and several benzoate derivatives varying in the nature and the position of the substituent on the benzoyl group were prepared and analysed. TBC clearly gives the broadest application range, and among the different benzoate esters the best selectivity was generally obtained with either the 4-methoxybenzoate or the 4-methylbenzoate derivatives. Based on these results, some empirical rules could be formulated for optimizing the enantiomeric separation of racemic alcohols, which make up one of the most important classes of chemical substances used as drugs and biocides, or as building blocks for their synthesis. An application of this approach to the preparative separation of the enantiomers of a drug intermediate is also shown. Chirality 10:492-498, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 43
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 507-512 
    ISSN: 0899-0042
    Keywords: chiroptical method ; drug analysis ; β-lactam antibiotics ; CD spectroscopy ; human fluids ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A study of the applicability of circular dichroism (CD) for the determination of drug levels in human serum is described and a new method for the quantitative determination of optically active absorbing drugs having Cotton effects at wavelengths above 250 nm in human serum and/or plasma is proposed. The principal advantages of this method are speed, economy, and simplicity, no derivatization or chromatographic separation steps being needed. The validity of the CD determination was confirmed by analysis of variance, β-lactam antibiotics being chosen as model drugs. In addition, the validation studies performed confirm the accuracy and precision of the proposed method. For β-lactam antibiotics lacking Cotton effects above 250 nm, an alternative method based on the extraction of the drug from serum is considered. Chirality 10:507-512, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 44
    ISSN: 0899-0042
    Keywords: chiral HPLC ; quantitative substituent effect ; recognition mechanism ; fluorene derivative-chiral separation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The chromatographic parameters for 12 structurally related compounds in the 4a-methyl-2,3,4,4a-tetrahydro-1H-fluorene and 4a-methyl-1,2,3,4,4a,9a-hexahydro-fluoren-9-one series are reported on CTA-I and Chiralcel OJ chiral stationary phases. Arrangement of the k' values according to configurationally related enantiomer series (Class I and Class II) and not according to the actual order of elution, allows the treatment of the data by linear correlation with structure and substituent effect. A detailed analysis of the capacity factor variation with respect to the structural changes shows clearly that the framework and substitution effects do not result in the same response on the two cellulose ester chiral stationary phases. More interestingly, it emerges that chiral discimination may be attributed to certain areas of the molecule, these areas being different in the interaction within CTA-I and Chiralcel OJ. Furthermore, our analysis points out the relevance of attempting to develop quantitative relationships for configurationally related series of enantiomers (in our case Class I and Class II), the main effort being devoted to the understanding of the capacity factor variation in each class rather than of the α values, which are derived entities. Chirality 10:522-527, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 45
    ISSN: 0899-0042
    Keywords: asymmetric hydrogenation ; non-coded amino acids ; enantioselectivity ; dipeptides ; diastereoselectivity ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The enantiomers of Propranolol, Pindolol, and Carazolol, well-known β-blockers, have been used to prepare cationic aminophosphine phosphinite rhodium complexes. Propraphos-Rh and Pindophos-Rh are very efficient catalysts in the asymmetric hydrogenation of N-Boc-protected unusual dehydroamino acid derivatives. Carazolol-Rh is less suitable in both activity and enantioselectivity. Under the same conditions, N-Boc-protected dehydrodipeptides are hydrogenated with diastereoselectivities between 70 and 90% de. Chirality 10:535-539, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 46
    ISSN: 0899-0042
    Keywords: quinuclidine derivatives ; chromatographic separation ; borane complexes ; fractional crystallization ; resolution ; X-ray crystallography ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The four stereoisomers of the antimuscarinic 3-(2,3-dihydrobenzofuran-2-yl)quinuclidine have been prepared by a method involving chromatographic separation of the racemic diastereoisomers as borane complexes. The relative and absolute configurations of the stereoisomers were determined by X-ray crystallographic methods. The crystal structure of (2′R,3R)-3-(2,3-dihydrobenzofuran-2-yl)quinuclidine · HCl · H2O contains two independent molecules with different conformations of both the quinuclidine moiety and the dihydrofuran ring. Chirality 10:813-820, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 47
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 1-2 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: No abstract.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 48
    ISSN: 0899-0042
    Keywords: α-hydroxy acids ; chiral stationary phases ; enantiomer resolution ; copper ternary complexes ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Direct separation of several α-hydroxy acid racemic mixtures was performed by the aid of ligand exchange chromatography using L-hydroxyproline chemically bound to silica stationary phase and aqueous solutions of copper (II) sulphate as a mobile phase. The elution order of the D- and L-enantiomers of α-hydroxy acids is interpreted in terms of a modified Davankov's rule. Several aspects of the Davankov's model of selectand-Cu(II)-selector ternary complexes are discussed based on the theoretical calculations within the quantum mechanical semiempirical and density functional theories. Chirality 10:821-830, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 49
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 3-7 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: No abstract.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 50
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 8-13 
    ISSN: 0899-0042
    Keywords: stereochemistry ; ion channel proteins ; nAChR ; K+ channels ; subunit arrangement ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Studies of ion channel proteins present many special challenges, including the potential for novel stereochemical phenomena. Here we describe several examples in which modern studies of ion channels have involved or made use of stereochemistry. Chirality 10:8-13, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 51
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 14-23 
    ISSN: 0899-0042
    Keywords: biological signalling ; ristocetin A ; cooperativity ; dimerization ; asymmetry ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The self-regulation of biological signalling receptors via homodimerization is discussed in relation to the symmetry changes occurring when these receptors bind their target ligand. The idea of positive and negative cooperativity between dimerization and ligand binding, mediated by changes in the symmetry of the system, as a source of signalling control is considered; and an analogy made with the homodimerization of a glycopeptide antibiotic, ristocetin A, which displays negative cooperativity. Finally, the regulation of the bacterial aspartate receptor and the human growth hormone receptor is discussed as a function of ligand-induced asymmetry. Chirality 10:14-23, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 52
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 24-27 
    ISSN: 0899-0042
    Keywords: homochirality ; origins of chirality ; spontaneous resolution ; molecular evolution ; racemic state ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: An evaluation of some common misconceptions of the racemic state in combination with an articulation of principles for the spontaneous generation and amplification of chirality leads to the conclusion that homochirality in nature is a stereochemical imperative. Chirality 10:24-27, 1998. © 1998 Wiley-Liss, Inc.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 53
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 28-34 
    ISSN: 0899-0042
    Keywords: collagen ; nuclear magnetic resonance (NMR) ; nuclear Overhauser effect (NOE) ; stereospecific assignment ; triple-helix ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: An improved model-based method for the stereospecific assignment of prochiral centers in collagen-like triple-helical molecules is introduced. Using the concepts of reporter atoms and of ensemble NOEs, the proposed methodology extracts the stereochemical information contained in the chiral elements of triple-helices and transfers it to prochiral centers with nondegenerate proton resonances. The improved approach has been successfully validated using -(Gly-Pro-Hyp)n- triple-helices for which the stereospecific assignment was previously obtained with established techniques. We have applied our stereochemical characterization to novel peptoid containing triple-helices for which existing methods of stereospecific assignment can not be used for all the prochiral centers. In our approach, several different NOE measurements are employed to make a given stereospecific assignment. The multiple NOE comparisons allow internal cross checks, which reduce the chance of erroneous assignments caused by experimental artifacts including spin diffusion and bias from anisotropic rotational motions. In addition, the multiple NOE comparisons are useful in overcoming problems associated with resonance overlap often encountered in the 1H-NMR spectra of collagen-like molecules. Our stereochemical analysis is anticipated to improve the precision and accuracy of the characterization of collagen-like triple-helices through a better correlation of structures with their 1H-NMR spectra. Chirality 10:28-34, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 54
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 35-40 
    ISSN: 0899-0042
    Keywords: de novo design ; self-assembly ; metalloproteins ; diastereoselection ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The stereochemical consequences of the metal-ion assisted self-assembly of parallel three-helix peptide bundles are investigated. Chiral induction in the self-assembly of systems containing extensive protein secondary structure is compared with the racemic synthesis of short metallopeptides. Isolation and characterization of the individual stereoisomers of an exchange-inert metalloprotein provide structural insights into analogous exchange-labile systems. Chirality 10:35-40, 1998. © 1998 Wiley-Liss,Inc.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 55
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 10 (1998), S. 195-209 
    ISSN: 0899-0042
    Keywords: molecular imprinting ; molecular recognition ; chirality ; chromatography ; catalysis ; biosensor ; immunoassay ; antibody mimic ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Molecular imprinting is a technique for the fabrication of biomimetic polymeric recognition sites or “plastic antibodies/receptors” which is attracting rapidly increasing interest. By this technology, recognition matrices can be prepared which possess high substrate selectivity and specificity. In the development of this technology, several applications have been foreseen in which imprinted materials may be exchanged for natural recognition elements. Thus, molecularly imprinted polymers have been used as antibody/receptor binding mimics in immunoassay-type analyses, as enzyme mimics in catalytic applications and as recognition matrices in biosensors. The best developed application area for imprinted materials, though, has been as stationary phases for chromatography, in general, and chiral chromatography, in particular. This review seeks to highlight some of the more intriguing advantages of the technique as well as pointing out some of the difficulties encountered. The prospects for future development will also be considered. Chirality 10:195-209, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 56