Physical Sciences and Mathematics Commons^™

A Biochemical Nickel(I) State Supports Nucleophilic Alkyl Addition: A Roadmap For Methyl Reactivity In Acetyl Coenzyme A Synthase, A. C. Manesis, B. W. Musselman, Breena C. Keegan, Jason M. Shearer, N. Lehnert, H. S. Shafaat

Chemistry Faculty Research

Nickel-containing enzymes such as methyl coenzyme M reductase (MCR) and carbon monoxide dehydrogenase/acetyl coenzyme A synthase (CODH/ACS) play a critical role in global energy conversion reactions, with significant contributions to carbon-centered processes. These enzymes are implied to cycle through a series of nickel-based organometallic intermediates during catalysis, though identification of these intermediates remains challenging. In this work, we have developed and characterized a nickel-containing metalloprotein that models the methyl-bound organometallic intermediates proposed in the native enzymes. Using a nickel(I)-substituted azurin mutant, we demonstrate that alkyl binding occurs via nucleophilic addition of methyl iodide as a methyl donor. The paramagnetic Ni …