Fast Time Scale Dynamics of Protein Backbones:  NMR Relaxation Methods, Applications, and Functional Consequences

Jarymowycz, Virginia A; Stone, Martin J.

doi:10.1021/cr040421p

Cited by 384 publications

(430 citation statements)

References 410 publications

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“…25 ), are non-zero and they can be calculated analytically as Lorentzian spectral densities, each defined by width 1/τ K . When the ordering potential is axially symmetric, , again only diagonal terms persist, but they are given by infinite sums of Lorentzian spectral densities which are defined in terms of eigenvalues 1/ τ i of the diffusion operator, and weighing factors c K,i , such that: (8) The eigevalues 1/τ i represent modes of motion of the system, in accordance with the parameter range considered. Note that although in principle the number of terms in eq 8 is infinite in practice a finite number of terms is sufficient for numerical convergence of the solution.…”

Section: The Slowly Relaxing Local Structure (Srls) Modelmentioning

confidence: 99%

An Improved Picture of Methyl Dynamics in Proteins from Slowly Relaxing Local Structure Analysis of ²H Spin Relaxation

et al. 2007

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Protein dynamics is intimately related to biological function. Core dynamics is usually studied with 2 H spin relaxation of the 13 CDH 2 group, analyzed traditionally with the model-free (MF) approach. We showed recently that MF is oversimplified in several respects. This includes the assumption that the local motion of the dynamic probe and the global motion of the protein are decoupled, the local geometry is simple, and the local ordering has axial symmetry. Because of these simplifications MF has yielded a puzzling picture where the methyl rotation axis is moving rapidly with amplitudes ranging from nearly complete disorder to nearly complete order in tightly packed protein cores. Our conclusions emerged from applying to methyl dynamics in proteins the slowly relaxing local structure (SRLS) approach of Polimeno and Freed (J. Phys. Chem. 1995, 99, 1099), which can be considered the generalization of MF, with all the simplifications mentioned above removed. The SRLS picture derived here for the B1 immunoglobulin binding domain of peptostreptococcal protein L, studied over the temperature range of 15 − 45 °C, is fundamentally different from the MF picture. Thus, methyl dynamics is characterized structurally by rhombic local potentials with varying symmetries, and dynamically by tenfold slower rates of local motion. On average potential rhombicity decreases, mode-coupling increases and the rate of local motion increases with increasing temperature. The average activation energy for local motion is 2.0 ± 0.2 kcal/mol. Mode-coupling affects the analysis even at 15 o C. The accuracy of the results is improved by including in the experimental data set relaxation rates associated with rank 2 coherences. Keywords slowly relaxing local structure; methyl dynamics in proteins; NMR spin relaxation in proteins

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Section: The Slowly Relaxing Local Structure (Srls) Modelmentioning

confidence: 99%

An Improved Picture of Methyl Dynamics in Proteins from Slowly Relaxing Local Structure Analysis of ²H Spin Relaxation

et al. 2007

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“…Proteins mostly undergo submillisecond time scale conformational changes upon ligand binding, and it is of importance to recognize the change of dynamic properties associated with this process. NMR is a well established technique to provide the site-specific motional information with exquisite time resolution (78). Therefore, insights obtained from dynamics may have potential implications in understanding of the biological functions (76).…”

Section: Nmr Characterizations Of the Apo-and Holo-forms Of E Colimentioning

confidence: 99%

Solution Structures and Backbone Dynamics of a Flavodoxin MioC from Escherichia coli in both Apo- and Holo-forms

Zhang

et al. 2006

Journal of Biological Chemistry

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Flavodoxins play central roles in the electron transfer involving various biological processes in microorganisms. The mioC gene of Escherichia coli encodes a 16-kDa flavodoxin and locates next to the chromosomal replication initiation origin (oriC). Extensive researches have been carried out to investigate the relationship between mioC transcription and replication initiation. Recently, the MioC protein was proposed to be essential for the biotin synthase activity in vitro. Nevertheless, the exact role of MioC in biotin synthesis and its physiological function in vivo remain elusive. In order to understand the molecular basis of the biological functions of MioC and the cofactor-binding mechanisms of flavodoxins, we have determined the solution structures of both the apo-and holo-forms of E. coli MioC protein at high resolution by nuclear magnetic resonance spectroscopy. The overall structures of both forms consist of an ␣/␤ sandwich, which highly resembles the classical flavodoxin fold. However, significant diversities are observed between the two forms, especially the stabilization of the FMN-binding loops and the notable extension of secondary structures upon FMN binding. Structural comparison reveals fewer negative charged and aromatic residues near the FMN-binding site of MioC, as compared with that of flavodoxin 1 from E. coli, which may affect both the redox potentials and the redox partner interactions. Furthermore, the backbone dynamics studies reveal the conformational flexibility at different time scales for both apo-and holo-forms of MioC, which may play important roles for cofactor binding and electron transfer.Flavodoxins are small FMN-binding proteins found mainly in prokaryotes that are involved in the electron transfer chain reactions of various biological processes, including photosynthesis (1, 2), nitrate reduction (3), methionine synthesis (4 -7), biotin synthesis (8 -11), and activation of certain enzymes, such as pyruvate-formate lyase (13) and (E)-4-hydroxy-3-methylbutyl-2-enyl pyrophosphate synthase (14). It has been established by potentiometry that electrons flow from NADPH to flavodoxin reductase and then to flavodoxin, which subsequently transfers the electron to the downstream targets (15). Eukaryotes and most prokaryotes also contain proteins carrying domains homologous to flavodoxins and flavodoxin reductase in a single polypeptide chain, such as the NADPH-cytochrome P450 oxidoreductase (CPR) 2 (16, 17), nitric-oxide synthase (NOS) (18), methionine synthase reductase (19), and sulfite reductase (20,21). These domains function in a similar fashion as the flavodoxins and flavodoxin reductase proteins in prokaryotic cells. Extensive efforts have been devoted to understanding the cofactor binding, redox partner interaction, and electron transfer mechanisms of flavodoxins and flavodoxinlike domains as well as the folding and stability of these proteins (22-26). However, the detailed mechanisms are not clear yet and remain to be further elucidated.Flavodoxins are classified into the long-...

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“…Backbone amide order parameters have been measured for more than 200 proteins and used to quantify changes in conformational flexibility associated with protein folding, molecular recognition, and catalysis. 4 Values of S 2 obtained from protein molecular dynamics (MD) simulations have been compared to those obtained from experiments to validate 6,7 and improve 8,9 MD simulations, and to aid in the interpretation of experiments. 10,11 Ubiquitin is a 76-residue protein that has been used as a model system for experimental and computational studies of protein structure and dynamics.…”

Section: Introductionmentioning

confidence: 99%

Microsecond Molecular Dynamics Simulation Shows Effect of Slow Loop Dynamics on Backbone Amide Order Parameters of Proteins

et al. 2008

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A molecular-level understanding of the function of a protein requires knowledge of both its structural and dynamic properties. NMR spectroscopy allows the measurement of generalized order parameters that provide an atomistic description of picosecond and nanosecond fluctuations in protein structure. Molecular dynamics (MD) simulation provides a complementary approach to the study of protein dynamics on similar time scales. Comparisons between NMR spectroscopy and MD simulations can be used to interpret experimental results and to improve the quality of simulation-related force fields and integration methods. However, apparent systematic discrepancies between order parameters extracted from simulations and experiments are common, particularly for elements of noncanonical secondary structure. In this paper, results from a 1.2 µs explicit solvent MD simulation of the protein ubiquitin are compared with previously determined backbone order parameters derived from NMR relaxation experiments [Tjandra, N.; Feller, S. E.; Pastor, R. W.; Bax, A. J. Am. Chem. Soc. 1995, 117, 12562-12566]. The simulation reveals fluctuations in three loop regions that occur on time scales comparable to or longer than that of the overall rotational diffusion of ubiquitin and whose effects would not be apparent in experimentally derived order parameters. A coupled analysis of internal and overall motion yields simulated order parameters substantially closer to the experimentally determined values than is the case for a conventional analysis of internal motion alone. Improved agreement between simulation and experiment also is encouraging from the viewpoint of assessing the accuracy of long MD simulations.

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Fast Time Scale Dynamics of Protein Backbones: NMR Relaxation Methods, Applications, and Functional Consequences

Cited by 384 publications

References 410 publications

An Improved Picture of Methyl Dynamics in Proteins from Slowly Relaxing Local Structure Analysis of ²H Spin Relaxation

An Improved Picture of Methyl Dynamics in Proteins from Slowly Relaxing Local Structure Analysis of ²H Spin Relaxation

Solution Structures and Backbone Dynamics of a Flavodoxin MioC from Escherichia coli in both Apo- and Holo-forms

Microsecond Molecular Dynamics Simulation Shows Effect of Slow Loop Dynamics on Backbone Amide Order Parameters of Proteins

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Fast Time Scale Dynamics of Protein Backbones: NMR Relaxation Methods, Applications, and Functional Consequences

Cited by 384 publications

References 410 publications

An Improved Picture of Methyl Dynamics in Proteins from Slowly Relaxing Local Structure Analysis of 2H Spin Relaxation

An Improved Picture of Methyl Dynamics in Proteins from Slowly Relaxing Local Structure Analysis of 2H Spin Relaxation

Solution Structures and Backbone Dynamics of a Flavodoxin MioC from Escherichia coli in both Apo- and Holo-forms

Microsecond Molecular Dynamics Simulation Shows Effect of Slow Loop Dynamics on Backbone Amide Order Parameters of Proteins

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An Improved Picture of Methyl Dynamics in Proteins from Slowly Relaxing Local Structure Analysis of ²H Spin Relaxation

An Improved Picture of Methyl Dynamics in Proteins from Slowly Relaxing Local Structure Analysis of ²H Spin Relaxation