National Institute of General Medical Sciences 5R35GM122595-11

Mechanisms of Iron-Sulfur Dependent Reactions

This NIH-funded project studies radical SAM enzymes that catalyze methylation reactions important for antibiotic biosynthesis and resistance, aiming to understand their mechanisms and structures.

Description

The project focuses on the study of radical S-adenosylmethionine enzymes, which are iron-sulfur-dependent proteins that catalyze a variety of cellular reactions involving free radicals. These enzymes are involved in methylation of small molecules, DNA, RNA, proteins, and lipids, which are important in human health, including antibiotic biosynthesis and resistance. The research aims to understand the mechanisms of radical SAM methylases, which include three classes based on structural architecture and mechanism: Class A (Cys dyad), Class B (cobalamin cofactors), and Class C (two SAM molecules). The work will involve structural studies of these enzymes with substrates, cofactors, and intermediates, with a focus on enzymes involved in antibiotic resistance and biosynthesis.

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