研究・研究者
研究会・セミナー
| 演 題 | 「Molecular Dynamics Simulations of NAD+-induced Domain Closure in Horse Liver Alcohol Dehydrogenase」 |
|---|---|
| 日 時 | 2007年04月26日(木) 14:00 |
| 講演者 | Prof. Steven Hayward University of East Anglia, School of Biological Sciences and School of Computing Sciences |
| 場 所 | 計算科学研究センター2階 会議室 |
| 概 要 | Horse liver alcohol dehydrogenase is a homodimer, the protomer having a coenzyme-binding domain and a catalytic domain. Using all available X-ray structures and 50 nanoseconds of molecular dynamics simulations, the mechanism of NAD+-induced domain closure was investigated. When the loop at the domain interface was modelled to its conformation in the closed structure, the NAD+-induced domain closure from the open structure could be simulated with remarkable accuracy. Native interactions in the closed structure between Arg369, Arg47, His51, Ala317, Phe319 and NAD+ were seen to form at different stages during domain closure. Removal of the Arg369 side-chain charge resulted in the loss of the tendency to close so verifying that specific interactions do help drive the domains closed. Further simulations and a careful analysis of X-ray structures suggest that the loop prevents domain closure in the absence of NAD+, and a cooperative mechanism operates between the subunits for domain closure. This cooperative mechanism explains the role of the loop as a block to closure, as in the absence of NAD+ it would prevent the occurrence of an unliganded closed subunit when the other subunit closes upon NAD+. These results combined with previous results on citrate synthase suggest that in some domain enzymes there are mechanisms that keep domains open in the absence of a functional ligand for reasons of efficiency. |
| お問合せ先 | 平田 文男、信定 克幸（理論・計算分子科学研究領域） |
