BBMB Research Seminars

Dr. Mishtu Dey
University of Michigan Medical School
“A Structural, Spectroscopic and Kinetic Approach Towards Understanding the Mechanism of Biological Methane Formation"

1414 Molecular Biology Buidling
4:40 p.m.

Abstract:

Methyl-Coenzyme M Reductase (MCR) from methanogenic archaea catalyzes the final step in the biological synthesis of methane. Using Coenzyme B (CoBSH) as the two-electron donor, MCR reduces methyl-coenzyme M (methyl-SCoM) to methane and the mixed disulfide, CoBS-SCoM. MCR contains Coenzyme F430, an essential redoxactive nickel tetrahydrocorphin, at its active site. The active form of MCR, denoted MCRred1, contains Ni(I)-F430. Two apparently competing mechanisms have been proposed for methane synthesis: one involves an organometallic methyl-Ni(III) intermediate, while the other includes a methyl radical. We have performed rapid kinetic, spectroscopic, and crystallographic studies aimed at observing catalytic intermediates in the MCR reaction cycle. We have trapped and characterized the methyl-Ni intermediate as well as several other alkyl-Ni species and demonstrated that the methyl-Ni can be converted to methane with concomitant regeneration of the active enzyme. Recent studies have focused on characterizing a novel radical intermediate, and on crystallizing and determining the structure of the active Ni(I) and alkyl-Ni species. Based on these studies, we propose a significantly revised mechanism for methane formation that includes both methyl-Ni and methyl radical. Our mechanistic studies are providing insights into the biological role of nickel, which are important to the areas of microbiology, biochemistry, and bioinorganic chemistry.