研究・研究者
研究会・セミナー
| 演 題 | 「Excited states and (NMR) relaxation: Mapping protein energy landscapes by relaxation dispersion」 |
|---|---|
| 日 時 | 2007年08月22日(水) 16:00 |
| 講演者 | Prof. Peter E. Wright (Department of Molecular Biology, The Scripps Research Institute, La Jolla, California) |
| 場 所 | 岡崎コンファレンスセンター 中会議室 |
| 概 要 | NMR is a widely used method for determining the three-dimensional structures of proteins and other biomolecules in solution. However, protein structures are not static, and molecular motions are central to their biological functions. It is essential to move beyond our largely static view of protein structure towards an understanding of the dynamics and thermodynamics of conformational change and their relationship to protein function. NMR relaxation experiments provide a powerful approach to direct experimental characterization of protein dynamics on a broad range of time scales, ranging from ps to ms, and allow direct mapping of the protein energy landscape. Recently developed relaxation dispersion experiments permit quantitative analysis of the dynamics and thermodynamics of slow conformational fluctuations in proteins, of the mechanisms of protein folding, and of the kinetics of protein-ligand interactions and coupled folding and binding events. Applications of NMR to study the role of protein motions in the catalytic function of the enzyme dihydrofolate reductase (DHFR) will be described. Our experiments reveal active site conformational fluctuations on a time scale that is directly relevant to the structural transitions involved in progression through the catalytic cycle. Flexibility in the active site loops appears to be harnessed by the enzyme to control the flux of substrate, product, and cofactor, and to correctly position the reactants in the active site prior to the hydride transfer step. Progress through the catalytic cycle involves a dynamic energy landscape, where each intermediate populates excited states in which the protein conformation corresponds to that of the preceding or following intermediate in the cycle. NMR also provides detailed insights into the coupled folding and binding processes that mediate the physiological functions of intrinsically disordered proteins. In particular, relaxation dispersion measurements provide an especially powerful approach for mapping the folding pathway, providing novel insights into the mechanism of coupled folding and binding, and allowing structural characterization of transient encounter complexes. Finally, applications of NMR relaxation experiments to characterize the protein folding landscape will be discussed. |
| その他 | 午後４時より５時過ぎまで（コーヒータイムは３時半から） |
