The carboxylate "gripper" of the substrate is critical for C-4 stereo-inversion by UDP-glucuronic acid 4-epimerase.

ABSTRACT: UDP-glucuronic acid 4-epimerase (UGAepi) catalyzes the NAD⁺-dependent interconversion of UDP-glucuronic acid (UDP-GlcA) and UDP-galacturonic acid (UDP-GalA) through a mechanism involving C4-oxidation, 4-keto-intermediate rotation, and subsequent reduction. Here, the functional significance of the substrate's carboxylate group in the epimerization process was investigated using UDP-4-keto-pentose, an analogous intermediate that lacks a carboxylate moiety. Site-directed mutations were introduced into UGAepi from Bacillus cereus (BcUGAepi) to increase substrate binding pocket flexibility, enabling the variant enzymes to accommodate UDP-4-keto-pentose more efficiently than the wild-type does. Although these BcUGAepi variants partially maintained nonstereospecific C4-epimerization ac

SUBMITTER: Borg AJE 

PROVIDER: S-EPMC12338863 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature