Early stages of energy transduction by myosin: Roles of Arg in switch I, of Glu in switch II, and of the salt-bridge between them

Hirofumi Onishi, Takashi Ohki, Naoki Mochizuki, Manuel F. Morales

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

On the basis of the crystallographic snapshots of Rayment and his collaborators [Fisher, A. J., Smith, C. A., Thoden, J. B., Smith, R., Sutoh, K., Holden, H. M., & Rayment, I. (1995) Biochemistry 34, 8960-8972], we have understood some basic principles about the early stages of myosin catalysis, namely, ATP is drawn into the active site, over which the cleft closes. Catalyzed hydrolysis occurs, and the first product (orthophosphate) is released from the backdoor of the cleft. In the cleft-closing process, the active site incidentally signals its movement to a particular remote tryptophan residue, Trp-512. In this work, we expand on some of these ideas to rationalize the behavior of a mutated system in action. From the behavior of recombinant myosin systems in which Arg-247 and Glu-470 were substituted in several ways, we draw the conclusions that (i) the force between Arg-247 and γ-phosphate of ATP may assist in closing the cleft, and incidentally in signaling to the remote Trp, and (ii) in catalysis, Glu-470 is involved in holding the lytic H2O (w1). We also propose that w1 and also a second water, w2, enter into a structure that bridges Glu-470 and the γ-phosphate of bound ATP, and at the same time positions w1 for its in-line hydrolytic attack.

Original languageEnglish
Pages (from-to)15339-15344
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number24
DOIs
Publication statusPublished - 2002 Nov 26
Externally publishedYes

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Myosins
Salts
Adenosine Triphosphate
Phosphates
Catalysis
Catalytic Domain
Tryptophan
Biochemistry
Hydrolysis
Water

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Early stages of energy transduction by myosin : Roles of Arg in switch I, of Glu in switch II, and of the salt-bridge between them. / Onishi, Hirofumi; Ohki, Takashi; Mochizuki, Naoki; Morales, Manuel F.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 24, 26.11.2002, p. 15339-15344.

Research output: Contribution to journalArticle

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