부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.theochem.2005.10.019 Byline: Kazunori Yamanaka (a), Noriaki Okimoto (b), Saburo Neya (a), Masayuki Hata (a), Tyuji Hoshino (a)(c) Abstract: Not a single water molecule but a group of water molecules frequently play an important role to functionalize the enzymatic reaction of proteins. In this study, we carried out molecular dynamics (MD) simulations for four types of myosin-nucleotide complexes; the ATP and/or ADP/P.sub.i-bound myosins with the cleft open and/or close conformations. Computational results show a keen role of water molecules that are regulated by a salt-bridge formed between Arg238 in Switch I and Glu459 in Switch II. Before the ATP hydrolysis, Arg238 and Glu459 hold a lytic-water near ATP-[gamma] phosphate and close the salt-bridge to inhibit any other water to enter the ATPase pocket except one water that controls the orientation of the lytic-water facing to ATP. Once the salt-bridge is opened after ATP hydrolysis, a large number of water molecules are circulating in the ATPase pocket. Our results demonstrate that the access of water molecules is precisely controlled in the respective reaction step of the ATP hydrolysis cycle. Author Affiliation: (a) Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263-8522, Japan (b) Bioinformatics Group, GSC, RIKEN, 61-1 Ono-cho, Tsurumi, Yokohama 230-0046, Kanagawa, Japan (c) PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho Kawaguchi, Saitama, Japan Article History: Received 25 August 2005; Revised 4 October 2005; Accepted 7 October 2005