Conservation of Atypical Allostery in C. elegans UDP-Glucose Dehydrogenase.

ABSTRACT: Human UDP-glucose dehydrogenase (hUGDH) oxidizes uridine diphosphate (UDP)-glucose to UDP-glucuronic acid, an essential substrate in the phase II metabolism of drugs. The activity of hUGDH is controlled by an atypical allosteric mechanism in which the feedback inhibitor UDP-xylose competes with the substrate for the active site and triggers a buried allosteric switch to produce an inactive complex (E^Ω). Previous comparisons with a nonallosteric UGDH identified six large-to-small substitutions that produce packing defects in the protein core and provide the conformational flexibility necessary for the allosteric transition. Here, we test the hypothesis that these large-to-small substitutions form a motif that can be used to identify allosteric UGDHs. Caenorhabditis elegans

SUBMITTER: Beattie NR 

PROVIDER: S-EPMC6788056 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature