Molecular Basis for Peptide Nitration by a Novel Cytochrome P450 Enzyme in RiPP Biosynthesis.

ABSTRACT: RufO is a unique cytochrome P450 enzyme (CYP) involved in the biosynthesis of rufomycin, an antituberculosis cyclic peptide featuring an unusual nitrated tyrosine. Recent studies have clarified RufO's role in producing ribosomally synthesized and post-translationally modified peptides (RiPPs). Despite growing interest in nitrating enzymes and RiPP biosynthesis, the mechanism by which RufO recognizes and nitrates its pentapeptide substrate, MRYLH, remains poorly understood. In this study, we use a combination of spectroscopic, kinetic, and structural techniques to elucidate the molecular basis for peptide binding and heme-based nitration in RufO. Peptide binding is an endothermic process with a dissociation constant of 0.78 μM. Unlike most CYPs, RufO does not undergo the typical spin state

SUBMITTER: Nolan K 

PROVIDER: S-EPMC12186263 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature