Stereo-electronic control of reaction selectivity in short-chain dehydrogenases: Decarboxylation, epimerization, and dehydration

Sugar nucleotide–modifying enzymes of the short-chain dehydrogenase/reductase type use transient oxidation–reduction by a tightly bound nicotinamide cofactor as common strategy catalysis to promote diverse set reactions, including decarboxylation, single- or double-site epimerization, and dehydration. Although basic mechanistic principles have been worked out decades ago, finely tuned control reactivity selectivity in several these remains enigmatic. Recent evidence on uridine 5'-diphosphate (UDP)-glucuronic acid decarboxylases (UDP-xylose synthase, UDP-apiose/UDP-xylose synthase) UDP-glucuronic acid-4-epimerase suggests that stereo-electronic constraints established at enzyme's active site selectivity, timing catalytic reaction steps, conversion substrate toward different products. The idea is extended epimerases dehydratases deprotonate C? keto-hexose intermediate. human guanosine (GDP)-mannose 4,6-dehydratase was recently shown minimal machinery, exactly predicted earlier from theoretical considerations, for ?-elimination water species.