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Orekhov, Vladislav Yu.; Arseniev, Alexander S.

doi:10.1023/a:1008362725909

Cited by 9 publications

(3 citation statements)

References 26 publications

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“…Order parameters are lowered for NHs of the N‐terminal Trp1–Gln3 and the C‐terminal Phl16, which might be explained by helix–coil transitions involving the helix ends (see e.g. [15,29]). The correlation times τ e for most of the NHs from the central part of Zrv‐IIB fall into a sub‐picosecond time‐scale (Fig.…”

Section: Resultsmentioning

confidence: 99%

Backbone dynamics of the channel‐forming antibiotic zervamicin IIB studied by ¹⁵N NMR relaxation

et al. 2001

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The backbone dynamics of the channel-forming peptide antibiotic zervamicin IIB (Zrv-IIB) in methanol were studied by 15 N nuclear magnetic resonance relaxation measurements at 11.7, 14.1 and 18.8 T magnetic fields. The anisotropic overall rotation of the peptide was characterized based on 15 N relaxation data and by hydrodynamic calculations.`Model-free' analysis of the relaxation data showed that the peptide is fairly rigid on a sub-nanosecond time-scale. The residues from the polar side of Zrv-IIB helix are involved in micro^millisecond time-scale conformational exchange. The conformational exchange observed might indicate intramolecular processes or specific intermolecular interactions of potential relevance to Zrv-IIB ion channel formation. ß 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

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Section: Resultsmentioning

confidence: 99%

Backbone dynamics of the channel‐forming antibiotic zervamicin IIB studied by ¹⁵N NMR relaxation

et al. 2001

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“…The correlation functions describing the internal dynamics of the backbone N-H vectors were calculated as where N is the number of snapshots and r j is the studied normalized vector in the jth snapshot. 35 The order parameter dependent on the time window w was calculated as 35 and its highest value S max 2 (w) ≡ max(S 2 (k,w)) k was used as a measure of the motional freedom on the time scale defined by w. The average value, S ave 2 (w), was also calculated. The backbone conformation was characterized by evaluating the torsion angles φ and ψ.…”

Section: Simulationmentioning

confidence: 99%

Backbone Motions of Free and Pheromone-Bound Major Urinary Protein I Studied by Molecular Dynamics Simulation

et al. 2007

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Molecular motions of free and pheromone-bound mouse major urinary protein I, previously investigated by NMR relaxation, were simulated in 30 ns molecular dynamics (MD) runs. The backbone flexibility was described in terms of order parameters and correlation times, commonly used in the NMR relaxation analysis. Special attention was paid to the effect of conformational changes on the nanosecond time scale. Time-dependent order parameters were determined in order to separate motions occurring on different time scales. As an alternative approach, slow conformational changes were identified from the backbone torsion angle variances, and "conformationally filtered" order parameters were calculated for well-defined conformation states. A comparison of the data obtained for the free and pheromone-bound protein showed that some residues are more rigid in the bound form, but a larger portion of the protein becomes more flexible upon the pheromone binding. This finding is in general agreement with the NMR results. The higher flexibility observed on the fast (fs-ps) time scale was typically observed for the residues exhibiting higher conformational freedom on the ns time scale. An inspection of the hydrogen bond network provided a structural explanation for the flexibility differences between the free and pheromone-bound proteins in the simulations.

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“…59 Care must be taken that residues with genuine exchange terms or large amplitude internal motions are not included in the initial description of the molecular diffusion parameters. 60 With this in mind, the COPED approach 59 was used to determine the diffusion tensor and rotational correlation time τ m through a comparison of the experimental local diffusion coefficients derived from relaxation data and the diffusion coefficients predicted from a hydrodynamic model. In this way, residues with significant contributions to relaxation rates from picosecond to nanosecond or microsecond to millisecond motions were identified and excluded from the initial calculations of the molecular diffusion parameters.…”

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confidence: 99%

A Distal Mutation Perturbs Dynamic Amino Acid Networks in Dihydrofolate Reductase

et al. 2013

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Correlated networks of amino acids have been proposed to play a fundamental role in allostery and enzyme catalysis. These networks of amino acids can be traced from surface-exposed residues all the way into the active site, and disruption of these networks can decrease enzyme activity. Substitution of the distal Gly121 residue in E.coli dihydrofolate reductase results in up to a 200-fold decrease in the hydride transfer rate despite the fact that the residue is located 15 Å from the active-site center. In the present study, NMR relaxation experiments are used to demonstrate that dynamics on the ps-ns and μs-ms timescales are changed significantly in the G121V mutant of dihydrofolate reductase. In particular, ps-ns timescale dynamics are decreased in the FG loop (containing the mutated residue 121) and the neighboring active-site loop (the Met20 loop) in the mutant compared to wild-type enzyme, suggesting that these loops are dynamically coupled. Changes in methyl order parameters reveal a pathway by which dynamic perturbations can be propagated more than 25 Å across the protein from the site of mutation. All of the enzyme complexes, including the model Michaelis complex with folate and NADP+ bound, assume an occluded ground state conformation, and we do not observe sampling of a higher energy closed conformation by 15N R2 relaxation dispersion. This is highly significant, since it is only in the closed conformation that the cofactor and substrate reactive centers are positioned for reaction. The mutation also impairs μs - ms timescale fluctuations that have been implicated in product release from the wild type enzyme. Our results are consistent with an important role for Gly121 in controlling protein dynamics critical for enzyme function and further validate the dynamic energy landscape hypothesis of enzyme catalysis.

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Untitled

Cited by 9 publications

References 26 publications

Backbone dynamics of the channel‐forming antibiotic zervamicin IIB studied by ¹⁵N NMR relaxation

Backbone dynamics of the channel‐forming antibiotic zervamicin IIB studied by ¹⁵N NMR relaxation

Backbone Motions of Free and Pheromone-Bound Major Urinary Protein I Studied by Molecular Dynamics Simulation

A Distal Mutation Perturbs Dynamic Amino Acid Networks in Dihydrofolate Reductase

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Untitled

Cited by 9 publications

References 26 publications

Backbone dynamics of the channel‐forming antibiotic zervamicin IIB studied by 15N NMR relaxation

Backbone dynamics of the channel‐forming antibiotic zervamicin IIB studied by 15N NMR relaxation

Backbone Motions of Free and Pheromone-Bound Major Urinary Protein I Studied by Molecular Dynamics Simulation

A Distal Mutation Perturbs Dynamic Amino Acid Networks in Dihydrofolate Reductase

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Backbone dynamics of the channel‐forming antibiotic zervamicin IIB studied by ¹⁵N NMR relaxation

Backbone dynamics of the channel‐forming antibiotic zervamicin IIB studied by ¹⁵N NMR relaxation