The reaction mechanism of methyl-coenzyme M reductase: How an enzyme enforces strict binding order

Wongnate, Thanyaporn; Ragsdale, Stephen W.

doi:10.1074/jbc.m115.636761

The reaction mechanism of methyl-coenzyme M reductase: How an enzyme enforces strict binding order

Journal Article · Tue Feb 17 00:00:00 EST 2015 · Journal of Biological Chemistry

DOI:https://doi.org/10.1074/jbc.m115.636761· OSTI ID:1348414

Wongnate, Thanyaporn ^[1]; Ragsdale, Stephen W. ^[2]

Univ. of Michigan, Ann Arbor, MI (United States); DOE Office of Scientific and Technical Information (OSTI)
Univ. of Michigan, Ann Arbor, MI (United States)

Methyl-coenzyme M reductase (MCR) is a nickel tetrahydrocorphinoid (coenzyme F430) containing enzyme involved in the biological synthesis and anaerobic oxidation of methane. MCR catalyzes the conversion of methyl-2-mercaptoethanesulfonate (methyl-SCoM) and N-7-mercaptoheptanoylthreonine phosphate (CoB₇SH) to CH₄ and the mixed disulfide CoBS-SCoM. In this study, the reaction of MCR from Methanothermobacter marburgensis, with its native substrates was investigated using static binding, chemical quench, and stopped-flow techniques. Rate constants were measured for each step in this strictly ordered ternary complex catalytic mechanism. Surprisingly, in the absence of the other substrate, MCR can bind either substrate; however, only one binary complex (MCR·methyl-SCoM) is productive whereas the other (MCR·CoB₇SH) is inhibitory. Moreover, the kinetic data demonstrate that binding of methyl-SCoM to the inhibitory MCR·CoB₇SH complex is highly disfavored (K_d = 56 mM). However, binding of CoB₇SH to the productive MCR·methyl-SCoM complex to form the active ternary complex (CoB₇SH·MCR(Ni^I)·CH₃SCoM) is highly favored (K_d = 79 μM). Only then can the chemical reaction occur (k_obs = 20 s^-1 at 25 °C), leading to rapid formation and dissociation of CH₄ leaving the binary product complex (MCR(Ni^II)·CoB₇S^-·SCoM), which undergoes electron transfer to regenerate Ni(I) and the final product CoBS-SCoM. In conclusion, this first rapid kinetics study of MCR with its natural substrates describes how an enzyme can enforce a strictly ordered ternary complex mechanism and serves as a template for identification of the reaction intermediates.

View Accepted Manuscript (DOE)

Research Organization:: Univ. of Michigan, Ann Arbor, MI (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: FG02-08ER15931

OSTI ID:: 1348414

Journal Information:: Journal of Biological Chemistry, Journal Name: Journal of Biological Chemistry Journal Issue: 15 Vol. 290; ISSN 0021-9258

Publisher:: American Society for Biochemistry and Molecular BiologyCopyright Statement

Country of Publication:: United States

Language:: English

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