α-Amino-β-carboxymuconate-ε-semialdehyde decarboxylase catalyzes enol/keto tautomerization of oxaloacetate.

ABSTRACT: ACMSD (α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase) is a key metalloenzyme critical for regulating de novo endogenous NAD⁺/NADH biosynthesis through the tryptophan-kynurenine pathway. This decarboxylase is a recognized target implicated in mitochondrial diseases and neurodegenerative disorders. However, unraveling its enzyme-substrate complex has been challenging due to its high catalytic efficiency. Here, we present a combined biochemical and structural study wherein we determined the crystal structure of ACMSD in complex with malonate. Our analysis revealed significant rearrangements in the active site, particularly in residues crucial for ACMS decarboxylation, including Arg51, Arg239∗ (a residue from an adjacent subunit), His228, and Trp194. Docking modeling studie

SUBMITTER: Yang Y 

PROVIDER: S-EPMC11650718 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature