Is myosin a 'back door' enzyme?

R. G. Yount, D. Lawson, I. Rayment, L. Yu, C. Berger, H. White, M. Reedy, M. Ferenczi, S. Ishiwata, M. Kushmerick, E. Reisler, S. Highsmith, C. Cremo

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

ATP has been modeled into the active site of chicken skeletal myosin subfragment-1 using the adenylate kinase · Ap5A structure as a starting reference. The resulting docked ATP · S1 structure is justified in that it rationalizes the photolabeling data from several ATP analogs. The γ- phosphate of ATP sits at the bottom of the active site pocket and is partially visible via a view along the prominent 50-kDa cleft of S1 but not when viewed from above the active site. It is postulated that actin binding promotes the movement of the P-loop and Arg-245 to allow P(i) from ATP to leave via a 'back-door' in the 50-kDa fragment while ADP is still bound at the active site. Such a mechanism can explain a number of experimental observations, including the kinetics of ATP hydrolysis, the nucleotide dependence of P(i) exchange into ATP, and the formation of stable myosin · ADP · vanadate complexes in muscle fibers.

Original languageEnglish
JournalBiophysical Journal
Volume68
Issue number4 SUPPL.
Publication statusPublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics

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    Yount, R. G., Lawson, D., Rayment, I., Yu, L., Berger, C., White, H., Reedy, M., Ferenczi, M., Ishiwata, S., Kushmerick, M., Reisler, E., Highsmith, S., & Cremo, C. (1995). Is myosin a 'back door' enzyme? Biophysical Journal, 68(4 SUPPL.).