Structural insights into the catalytic mechanism of the microcystin tailoring enzyme McyI.

ABSTRACT: The most common cyanotoxin microcystin is a cyclic heptapeptide produced by non-ribosomal peptide-polyketide synthetases and tailoring enzymes. The tailoring enzyme McyI, a 2-hydroxyacid dehydrogenase, converts (3-methyl)malate into (3-methyl)oxaloacetate to produce the non-proteinogenic amino acid (3-methyl)aspartate. The reaction is NAD(P)-dependent but the catalytic mechanism remains unclear. Here we describe the crystal structures of McyI at three states: bound with copurified NAD, cocrystallized with NAD/NADP, and cocrystallized with malate or the substrate analogue citrate. An McyI protomer has unusual three nicotinamide cofactor-binding sites, named the NAD-prebound, NADP specific, and non-specific sites. Biochemical studies confirmed the NADP preference during oxidoreductase reacti

SUBMITTER: Wang X 

PROVIDER: S-EPMC11977255 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature