Your email was sent successfully. Check your inbox.

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

Proceed reservation?

Export
  • 1
    Keywords: PATHWAYS ; DNA ; SEQUENCE ; NUCLEIC-ACIDS ; FREE-ENERGY ; MOLECULAR-DYNAMICS SIMULATIONS ; OPLS
    Type of Publication: Journal article published
    PubMed ID: 15053599
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: AB-INITIO ; ENERGIES ; PEPTIDE ; TIME ; ACTIVATION ; REDUCTION ; IONS ; CONTRAST ; PATTERNS ; ENERGY ; ELECTRON ; PEPTIDES ; MIGRATION ; BEHAVIOR ; GAS-PHASE ; DENSITY-FUNCTIONAL THEORY ; CHEMISTRY ; PATTERN ; analysis ; USA ; GAUSSIAN-BASIS SETS ; NOV ; SPIN ; ONE-ELECTRON ; CAPTURE-INDUCED DISSOCIATION ; CHARGED PROTEIN CATIONS ; CORRELATED MOLECULAR CALCULATIONS ; DISSOCIATION MASS-SPECTROMETRY ; HYDROGEN-ATOM ADDUCTS ; ION/ION REACTIONS ; N-C-ALPHA
    Abstract: Protonated peptides containing histidine or arginine residues and a free carboxyl group (His-Ala-Ile, His-Ala-Leu, Ala-His-Leu, Ala-Ala-His-Ala-Leu, His-Ala-Ala-Ala-Leu, and Arg-Ala-Ile) form stable anions upon collisional double electron transfer from Cs atoms at 50 keV kinetic energies. This unusual behavior is explained by hidden rearrangements occurring in peptide radical intermediates formed by transfer of the first electron. The rearrangements occur on a similar to 120 ns time scale determined by the radical flight time. Analysis of the conformational space for (His-Ala-Ile + H)(+) precursor cations identified two major conformer groups, 1a(+)-1m(+) and 5a(+)-5h(+), that differed in their H-bonding patterns and were calculated to collectively account for 39% and 60%, respectively, of the gas-phase ions. One-electron reduction in 1a(+) and 5a(+) triggers exothermic hydrogen atom migration from the terminal COOH group onto the His imidazole ring, forming imidazoline radical intermediates. The intermediate from 5a is characterized by its charge and spin distribution as a novel cation radical-COO- salt bridge. The intermediate from 1 a undergoes spontaneous isomerization by imidazoline N-H migration, re-forming the COOH group and accomplishing exothermic isomerization of the initial (3h)-imidazole radical to a (2h)-imidazole radical. An analogous unimolecular isomerization in simple imidazole and histidine radicals requires activation energies of 150 kJ mol(-1), and its occurrence in la and 5a is due to the promoting effect of the proximate COOH group. The rearrangement is substantially reduced in Ala-Leu-His due to an unfavorable spatial orientation of the imidazole and COOH groups and precluded in the absence of a free carboxyl group in His-Ala-Leu amide. In contrast to His-Ala-Ile and Arg-Ala-Ile, protonated Lys-Ala-Ile does not produce stable anions upon double electron transfer. The radical trapping properties of histidine residues are discussed
    Type of Publication: Journal article published
    PubMed ID: 18847261
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: screening ; COMPLEX ; COMPLEXES ; DYNAMICS ; SIMULATION ; ENERGY ; mass spectrometry ; NMR-SPECTROSCOPY ; SPECTROMETRY ; MASS-SPECTROMETRY ; MOLECULAR-DYNAMICS ; CHEMISTRY ; POLYSACCHARIDES ; HYDROLYSIS ; molecular dynamics ; OLIGOSACCHARIDE SYNTHESIS ; CRYSTALLOGRAPHY ; FLUORIDES ; GLYCOSIDE HYDROLASE ; HELICAL STRUCTURE
    Abstract: Glycosynthases are precise molecular instruments for making specifically linked oligosaccharides. X-ray crystallography screening of ligands bound to the 1,3(4)-beta-D-glucanase nucleophile mutant E115S of Phanerochaete chrysosporium Laminarinase 16A (Lam16A) showed that laminariheptaose (L7) bound in an arch with the reducing and nonreducing ends occupying either side of the catalytic cleft of the enzyme. The X-ray structure of Lam16A E115S in complex with alpha-laminariheptaosyl fluoride (alpha L7F) revealed how alpha L7F could make a nucleophilic attack upon itself. Indeed, when Lam16A E115S was allowed to react with alpha L7F the major product was a cyclic beta-1,3-heptaglucan, as shown by mass spectrometry. NMR confirmed uniquely beta-1,3-linkages and no reducing end. Molecular dynamics simulations indicate that the cyclic laminariheptaose molecule is not completely planar and that torsion angles at the glycosidic linkages fluctuate between two energy minima. This is the first report of a glycosynthase that joins the reducing and nonreducing ends of a single oligosaccharide and the first reported synthesis of cyclic beta-glucan
    Type of Publication: Journal article published
    PubMed ID: 20078120
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: ENERGIES ; ENVIRONMENT ; Germany ; PATHWAY ; PATHWAYS ; PROTEIN ; BASE ; PROTON ; WATER ; TRANSPORT ; ENERGY ; REGION ; PRODUCT ; STRUCTURAL-CHANGES ; REVEALS ; ORIENTATION ; AFFINITY ; BOND ; MOLECULAR-DYNAMICS ; PROTON-TRANSFER ; SCHIFF-BASE ; SOLID-STATE NMR ; CHARGE-DENSITY ; DARK-ADAPTED BACTERIORHODOPSIN ; DETERMINANTS ; ELECTRONIC POLARIZATION ; HALOBACTERIUM-HALOBIUM ; PROTEIN ENVIRONMENT ; RETINAL SCHIFF-BASE ; WATER-MOLECULES
    Abstract: The first proton transport step following photon absorption in bacteriorhodopsin is from the 13-cis retinal Schiff base to Asp85. Configurational and energetic determinants of this step are investigated here by performing quantum mechanical/molecular mechanical minimum-energy reaction-path calculations. The results suggest that retinal can pump protons when in the 13-cis, 15-anti conformation but not when 13-cis, 15-syn. Decomposition of the proton transfer energy profiles for various possible pathways reveals a conflict between the effect of the intrinsic proton affinities of the Schiff base and Asp85, which favors the neutral, product state (i.e., with Asp85 protonated), with the mainly electrostatic interaction between the protein environment with the reacting partners, which favors the ion pair reactant state (i.e., with retinal protonated). The rate-limiting proton-transfer barrier depends both on the relative orientations of the proton donor and acceptor groups and on the pathway followed by the proton; depending on these factors, the barrier may arise from breaking and forming of hydrogen bonds involving the Schiff base, Asp85, Asp212, and water w402, and from nonbonded interactions involving protein groups that respond to the charge rearrangements in the Schiff base region
    Type of Publication: Journal article published
    PubMed ID: 15521787
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: AB-INITIO ; PEPTIDE ; COMPLEX ; COMPLEXES ; BINDING ; SPECTROSCOPY ; ACID ; GAS ; PEPTIDES ; Jun ; PROTONATED PEPTIDES ; GAS-PHASE ; AMINO-ACID ; interaction ; PHASE ; CHARGE ; CATION-PI INTERACTIONS ; SALT ; density functional theory ; BIOLOGICAL MOLECULES ; FREE-ELECTRON LASER ; GLYCINE ZWITTERION ; MULTIPHOTON DISSOCIATION ; NA+ AFFINITIES ; PHOTODISSOCIATION SPECTROSCOPY ; RESONANCE MASS-SPECTROMETRY
    Abstract: Infrared multiple-photon dissociation spectroscopy is effected on the K+ tagged aromatic amino acids tyrosine and phenylalanine, as well as the K+ tagged peptides bradykinin fragment 1-5 and [Leu]-enkephalin. The fingerprint (800-1800 cm(-1)) infrared spectra of these species are compared to density-functional theory (DFT) calculated spectra to determine whether the complex is in the charge solvation (CS) or salt bridge (SB) (i.e. zwitterionic) configuration. For the aromatic amino acids the CS structure is favored and the tridentate N/O/ring structure is found to be the preferred binding geometry for K+. The experimental and theoretical evidence for bradykinin fragment 1-5 tagged with K+ suggests that the SB structure is favored; the calculations indicate a head-to-tail looped structure stabilized by a salt bridge between the protonated guanidine group and the deprotonated C-terminus, which allows K+ to sit in a binding pocket with five C=O electrostatic interactions. For K+ tagged [Leu]-enkephalin the spectroscopic evidence is not as clear. While the calculations clearly favor a CS structure and the observation of a weak carboxylic acid C=O stretching band in the infrared spectrum matches this finding, the prominence of a band at 1600 cm(-1) renders the analysis more ambiguous, and hence the presence of some salt bridge ions cannot be excluded. Another striking feature in the [Leu]-enkephalin spectrum is the high infrared activity of the tyrosine side-chain modes, which can be clearly identified from comparison to the [Tyr + K](+) experimental spectrum, but which is not reproduced by the DFT calculations
    Type of Publication: Journal article published
    PubMed ID: 15941293
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Keywords: AB-INITIO ; Germany ; PROTEIN ; PROTEINS ; EFFICIENCY ; MECHANISM ; FAMILY ; mechanisms ; BINDING ; ACID ; IDENTIFICATION ; MUTATION ; REGION ; MOLECULAR-MECHANISM ; FAMILIES ; VISUAL PIGMENTS ; QM/MM ; technique ; CONFIGURATION-INTERACTION PROCEDURE ; VARIETIES ; AGREEMENT ; SCC-DFTB METHOD ; AMINO-ACID SUBSTITUTIONS ; PHARAONIS PHOBORHODOPSIN ; PROTONATED SCHIFF-BASE ; QM/MM SIMULATIONS ; RETINAL CHROMOPHORE
    Abstract: The mechanism of color tuning in the rhodopsin family of proteins has been studied by comparing the optical properties of the light-driven proton pump bacteriorhodopsin (bR) and the light detector sensory rhodopsin II (sRII). Despite a high structural similarity, the maximal absorption is blue-shifted from 568 nm in bR to 497 nm in sRII. The molecular mechanism of this shift is still a matter of debate, and its clarification sheds light onto the general mechanisms of color tuning in retinal proteins. The calculations employ a combined quantum mechanical/molecular mechanical (QM/MM) technique, using a DFT-based method for ground state properties and the semiempirical OM2/MRCI method and ab initio SORCI method for excited state calculations. The high efficiency of the methodology has allowed us to study a wide variety of aspects including dynamical effects. The absorption shift as well as various mutation experiments and vibrational properties have been successfully reproduced. Our results indicate that several sources contribute to the spectral shift between bR and sRII. The main factors are the counterion region at the extracellular side of retinal and the amino acid composition of the binding pocket. Our analysis allows a distinction and identification of the different effects in detail and leads to a clear picture of the mechanism of color tuning, which is in good agreement with available experimental data
    Type of Publication: Journal article published
    PubMed ID: 16910676
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Keywords: AB-INITIO ; DENSITY-FUNCTIONAL-THEORY ; DFT ; PEPTIDE ; CELL ; PATHWAY ; PATHWAYS ; DENSITY ; POPULATION ; SITE ; SITES ; CONTRAST ; SEQUENCE ; MOLECULE ; SPECTROSCOPY ; ACID ; PLASMA ; COLLISION-INDUCED DISSOCIATION ; TANDEM MASS-SPECTROMETRY ; FRAGMENTS ; YOUNG ; CHEMISTRY ; INCREASE ; REARRANGEMENT ; USA ; AMINO-ACID-RESIDUES ; SURFACE-INDUCED DISSOCIATION ; FRAGMENT ; PRECURSOR ; AMIDE BOND-CLEAVAGE ; ACTIVATED DECOMPOSITION ; LEUCINE-ENKEPHALIN ; PEPTIDE IONS ; RADIATIVE DISSOCIATION
    Abstract: The gas-phase structures of the protonated pentapeptide Leu-enkephalin and its main collision-induced dissociation (CID) product ions, b(4) and a(4), are investigated by means of infrared multiple-photon dissociation (IR-MPD) spectroscopy and detailed molecular mechanics and density functional theory (DFT) calculations. Our combined experimental and theoretical approach allows accurate structural probing of the site of protonation and the rearrangement reactions that have taken place in CID. It is shown that the singly protonated Leu-enkephalin precursor is protonated on the N-terminus. The b(4) fragment ion forms two types of structures: linear isomers with a C-terminal oxazolone ring, as well as cyclic peptide structures. For the former structure, two sites of proton attachment are observed, on the N-terminus and on the oxazolone ring nitrogen, as shown in a previous communication (Polfer, N. C.; Oomens, J.; Suhai, S.; Paizs, B. J. Am. Chem. Soc. 2005, 127, 17154-17155). Upon leaving the ions for longer radiative cooling delays in the ion cyclotron resonance (ICR) cell prior to IR spectroscopic investigation, one observes a gradual decrease in the relative population of oxazolone-protonated b(4) and a corresponding increase in N-terminal-protonated b(4). This experimentally demonstrates that the mobile proton is transferred between two sites in a gas-phase peptide ion and allows one to rationalize how the proton moves around the molecule in the dissociation process. The a(4) fragment, which is predominantly formed via b(4), is also confirmed to adopt two types of structures: linear imine-type structures, and cyclic structures; the former isomers are exclusively protonated on the N-terminus in sharp contrast to b(4), where a mixture of protonation sites was found. The presence of cyclic b(4) and a(4) fragment ions is the first direct experimental proof that fully cyclic structures are formed in CID. These results suggest that their presence is significant, thus lending strong support to the recently discovered peptide fragmentation pathways (Harrison, A. G.; Young, A. B.; Bleiholder, B.; Suhai, S.; Paizs, B. J. Am. Chem. Soc. 2006, 128, 10364-10365) that result in scrambling of the amino acid sequence upon CID
    Type of Publication: Journal article published
    PubMed ID: 17428052
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Keywords: AB-INITIO ; PEPTIDE ; Germany ; MODEL ; PATHWAY ; PATHWAYS ; SITES ; MECHANISM ; IONS ; CONTRAST ; mechanisms ; SEQUENCE ; PROTON ; CLEAVAGE ; COLLISION-INDUCED DISSOCIATION ; TANDEM MASS-SPECTROMETRY ; fragmentation ; PEPTIDES ; AMINO-ACIDS ; PROTONATED PEPTIDES ; PROTEOMICS ; BOND ; GAS-PHASE ; CHEMISTRY ; AMIDE BOND ; INFRARED-SPECTROSCOPY ; ASPARTIC-ACID ; proton transfer ; USA ; peptide fragmentation ; SURFACE-INDUCED DISSOCIATION ; AMIDE BOND-CLEAVAGE ; Protons ; STATE ; MOBILE PROTON ; AMIDE ; FRAGMENTATION REACTIONS ; SALT-BRIDGE STRUCTURES ; TRYPTIC PEPTIDES
    Abstract: The mobile proton model (Dongre, A. R.; Jones, J. L.; Somogyi, A.; Wysocki, V. H. J. Am. Chem. Soc. 1996, 118, 8365-8374) of peptide fragmentation states that the ionizing protons play a critical role in the gas-phase fragmentation of protonated peptides upon collision-induced dissociation (CID). The model distinguishes two classes of peptide ions, those with or without easily mobilizable protons. For the former class mild excitation leads to proton transfer reactions which populate amide nitrogen protonation sites. This enables facile amide bond cleavage and thus the formation of b and y sequence ions. In contrast, the latter class of peptide ions contains strongly basic functionalities which sequester the ionizing protons, thereby often hindering formation of sequence ions. Here we describe the proton-driven amide bond cleavages necessary to produce b and y ions from peptide ions lacking easily mobilizable protons. We show that this important class of peptide ions fragments by different means from those with easily mobilizable protons. We present three new amide bond cleavage mechanisms which involve salt-bridge, anhydride, and imine enol intermediates, respectively. All three new mechanisms are less energetically demanding than the classical oxazolone b(n)-y(m) pathway. These mechanisms offer an explanation for the formation of b and y ions from peptide ions with sequestered ionizing protons which are routinely fragmented in large-scale proteomics experiments
    Type of Publication: Journal article published
    PubMed ID: 19746933
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
  • 10
    Keywords: AB-INITIO ; DENSITY-FUNCTIONAL-THEORY ; ENERGIES ; measurement ; PEPTIDE ; Germany ; SYSTEM ; MOLECULES ; MECHANISM ; FAMILY ; MOLECULE ; EQUIVALENT ; MOBILITY ; ENERGY ; ELECTROSPRAY ; SURFACE ; EXCHANGE ; PEPTIDES ; SERIES ; ENERGETICS ; PROTONATED PEPTIDES ; GAS-PHASE ; BASICITIES ; CONFORMATIONAL-CHANGES ; HYDROGEN-DEUTERIUM EXCHANGE ; HYDROGEN/DEUTERIUM EXCHANGE ; ION-MOLECULE REACTIONS ; IONIZATION MASS-SPECTROMETRY
    Abstract: A series of gas-phase experiments and extensive theoretical modeling was done on the family of singly protonated pepticles AARAA, Ac-AARAA, and AARAA-OMe. (AARAA)H+ underwent extensive H/D exchange with D2O, whereas the other two peptides with blocked termini did not, implying that a salt bridge was involved in the H/D exchange process. Ion mobility measurements and complementary molecular modeling unambiguously identified the 300 K structures of all three protonated pepticles as charge solvation structures, not salt bridges. High-level density functional theory calculations indicated the global minimum of (AARAA)H+ was a charge solvation structure with the lowest-energy salt bridge structure 4.8 kcal/mol higher in energy. Uptake of the first five water molecules of hydration at 260 K showed near identical propensities for all three pepticles consistent with a common structural motif. Quantitative measurements of DeltaHdegrees and DeltaSdegrees for the first two waters of hydration were very similar for all three pepticles, again suggestive of a common structure. A detailed search of the potential energy surface for the singly hydrated (AARAA)H+ using molecular mechanics and density functional theory approaches indicated a charge solvation structure was the global minimum, but now the lowest-energy salt bridge structure was only 1.8 kcal/mol higher in energy. Importantly, a low-energy transition state connecting the charge solvation and the salt bridge structures was found where the D2O molecule facilitated H/D exchange via the relay mechanism. This "relay" transition state was 7 kcal/mol below the (AARAA)H+ + D2O asymptotic energy, suggesting that facile H/D exchange could occur in this system. There was no equivalent low-lying relay mechanism transition state for the (Ac-AARAA)H+ and (AARAA-OMe)H+ peptides, consistent with the fact that H/D exchange was not observed. Hence, the combined experimental and theoretical methods confirmed that a salt bridge was involved in the H/D exchange by D2O of (AARAA)H+, but it existed only as a kinetic intermediate, not as a global minimum structure. These findings suggest that caution must be observed in drawing structural conclusions from H/D exchange only. A prescription is given here for understanding both the structural and H/D exchange mechanistic aspects of bare and singly hydrated peptides
    Type of Publication: Journal article published
    PubMed ID: 14599216
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...