2025-08-08 東京都立大学
図1.酵素反応の反応モデル
多くの酵素は反応部位の構造が変化することで、基質(反応物)を捉え、分子同士の結合や切断などの反応を起こす。この構造変化は多くの場合、非常に高速(ミリ秒)で大きな変化なので、この変化を正確にとらえることは難しい。
<関連情報>
- https://www.tmu.ac.jp/news/topics/37866.html
- https://www.tmu.ac.jp/extra/download.html?d=assets/files/download/news/press/20250808_tmupress.pdf
- https://pubs.acs.org/doi/10.1021/jacs.5c06502
多状態構造決定と動力学解析により、ユビキチンC末端ヒドロラーゼにおける独自のユビキチン認識メカニズムが明らかに Multistate Structure Determination and Dynamics Analysis Reveals a Unique Ubiquitin-Recognition Mechanism in Ubiquitin C-terminal Hydrolase
Mayu Okada,Yutaka Tateishi,Eri Nojiri,Tsutomu Mikawa,Sundaresan Rajesh,Hiroki Ogasa,Takumi Ueda,Hiromasa Yagi,Toshiyuki Kohno,Takanori Kigawa,Ichio Shimada,Peter Güntert,Yutaka Ito,and Teppei Ikeya
Journal of the American Chemical Society Published: August 6, 2025
DOI:https://doi.org/10.1021/jacs.5c06502
Abstract
Despite accumulating evidence that protein dynamics is indispensable for understanding the structural basis of biological activities, it remains challenging to visualize the spatial description of the dynamics and to associate transient conformations with their molecular functions. We have developed a new NMR protein structure determination method for the inference of multistate conformations using multiple types of NMR data, including paramagnetic NMR and residual dipolar couplings, as well as conventional NOEs. Integration of these data in the structure calculation permits delineating accurate ensemble structures of biomacromolecules. Applying the method to yeast ubiquitin hydrolase 1, we find large dynamics of its N-terminus (gating lid) and crossover loop surrounding the active site for ubiquitin-recognition and proteolysis. The N-terminus (gating lid) moves into and out of the crossover loop, suggesting their underlying functional significance. Our results, including those from biochemical analysis, show that large motion surrounding the active site contributes strongly to the efficiency of the enzymatic activity.
