The Mechanism of Inhibition of Pyruvate Formate Lyase by Methacrylate.

ABSTRACT: Pyruvate Formate Lyase (PFL) catalyzes acetyl transfer from pyruvate to coenzyme a by a mechanism involving multiple amino acid radicals. A post-translationally installed glycyl radical (G₇₃₄· in Escherichia coli) is essential for enzyme activity and two cysteines (C₄₁₈ and C₄₁₉) are proposed to form thiyl radicals during turnover, yet their unique roles in catalysis have not been directly demonstrated with both structural and electronic resolution. Methacrylate is an isostructural analog of pyruvate and an informative irreversible inhibitor of pfl. Here we demonstrate the mechanism of inhibition of pfl by methacrylate. Treatment of activated pfl with methacrylate results in the conversion of the G₇₃₄· to a new radical species, concomitant

SUBMITTER: Caceres JC 

PROVIDER: S-EPMC10591478 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature