Abstract
The ATP hydrolysis mechanism of myosin was studied using quantum chemical (QM) and molecular dynamics calculations. The initial model compound for QM calculations was constructed on the basis of the energy-minimized structure of the myosin(S1dc)-ATP complex, which was determined by molecular mechanics calculations. The result of QM calculations suggested that the ATP hydrolysis mechanism of myosin consists of a single elementary reaction in which a water molecule nucleophilically attacked gamma-phosphorus of ATP. In addition, we performed molecular dynamics simulations of the initial and final states of the ATP hydrolysis reaction, that is, the myosin-ATP and myosin-ADP.Pi complexes. These calculations revealed roles of several amino acid residues (Lys185, Thr186, Ser237, Arg238, and Glu459) in the ATPase pocket. Lys185 maintains the conformation of beta- and gamma-phosphate groups of ATP by forming the hydrogen bonds. Thr186 and Ser237 are coordinated to a Mg(2+) ion, which interacts with the phosphates of ATP and therefore contributes to the stabilization of the ATP structure. Arg238 and Glu459, which consisted of the gate of the ATPase pocket, retain the water molecule acting on the hydrolysis at the appropriate position for initiating the hydrolysis.
Full Text
The Full Text of this article is available as a PDF (908.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bagshaw C. R., Eccleston J. F., Eckstein F., Goody R. S., Gutfreund H., Trentham D. R. The magnesium ion-dependent adenosine triphosphatase of myosin. Two-step processes of adenosine triphosphate association and adenosine diphosphate dissociation. Biochem J. 1974 Aug;141(2):351–364. doi: 10.1042/bj1410351. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bernstein F. C., Koetzle T. F., Williams G. J., Meyer E. F., Jr, Brice M. D., Rodgers J. R., Kennard O., Shimanouchi T., Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977 May 25;112(3):535–542. doi: 10.1016/s0022-2836(77)80200-3. [DOI] [PubMed] [Google Scholar]
- Fisher A. J., Smith C. A., Thoden J. B., Smith R., Sutoh K., Holden H. M., Rayment I. X-ray structures of the myosin motor domain of Dictyostelium discoideum complexed with MgADP.BeFx and MgADP.AlF4-. Biochemistry. 1995 Jul 18;34(28):8960–8972. doi: 10.1021/bi00028a004. [DOI] [PubMed] [Google Scholar]
- Furch M., Fujita-Becker S., Geeves M. A., Holmes K. C., Manstein D. J. Role of the salt-bridge between switch-1 and switch-2 of Dictyostelium myosin. J Mol Biol. 1999 Jul 16;290(3):797–809. doi: 10.1006/jmbi.1999.2921. [DOI] [PubMed] [Google Scholar]
- Gulick A. M., Bauer C. B., Thoden J. B., Rayment I. X-ray structures of the MgADP, MgATPgammaS, and MgAMPPNP complexes of the Dictyostelium discoideum myosin motor domain. Biochemistry. 1997 Sep 30;36(39):11619–11628. doi: 10.1021/bi9712596. [DOI] [PubMed] [Google Scholar]
- Lee C, Yang W, Parr RG. Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B Condens Matter. 1988 Jan 15;37(2):785–789. doi: 10.1103/physrevb.37.785. [DOI] [PubMed] [Google Scholar]
- Li X. D., Rhodes T. E., Ikebe R., Kambara T., White H. D., Ikebe M. Effects of mutations in the gamma-phosphate binding site of myosin on its motor function. J Biol Chem. 1998 Oct 16;273(42):27404–27411. doi: 10.1074/jbc.273.42.27404. [DOI] [PubMed] [Google Scholar]
- Onishi H., Morales M. F., Kojima S., Katoh K., Fujiwara K. Smooth muscle myosin. Amino acid residues responsible for the hydrolysis of ATP. Adv Exp Med Biol. 1998;453:99–104. [PubMed] [Google Scholar]
- Rayment I., Rypniewski W. R., Schmidt-Bäse K., Smith R., Tomchick D. R., Benning M. M., Winkelmann D. A., Wesenberg G., Holden H. M. Three-dimensional structure of myosin subfragment-1: a molecular motor. Science. 1993 Jul 2;261(5117):50–58. doi: 10.1126/science.8316857. [DOI] [PubMed] [Google Scholar]
- Sasaki N., Sutoh K. Structure-mutation analysis of the ATPase site of Dictyostelium discoideum myosin II. Adv Biophys. 1998;35:1–24. [PubMed] [Google Scholar]
- Smith C. A., Rayment I. X-ray structure of the magnesium(II).ADP.vanadate complex of the Dictyostelium discoideum myosin motor domain to 1.9 A resolution. Biochemistry. 1996 Apr 30;35(17):5404–5417. doi: 10.1021/bi952633+. [DOI] [PubMed] [Google Scholar]