Allostery and Hysteresis Are Coupled in Human UDP-Glucose Dehydrogenase.

ABSTRACT: Human UDP-glucose dehydrogenase (hUGDH) is regulated by an atypical allosteric mechanism in which the feedback inhibitor UDP-xylose (UDP-Xyl) competes with the substrate for the active site. Binding of UDP-Xyl triggers the T131-loop/α6 allosteric switch, which converts the hexameric structure of hUGDH into an inactive, horseshoe-shaped complex (E^Ω). This allosteric transition buries residue A136 in the protein core to produce a subunit interface that favors the E^Ω structure. Here we use a methionine substitution to prevent the burial of A136 and trap the T131-loop/α6 switch in the active conformation. We show that hUGDH_A136M does not exhibit substrate cooperativity, which is strong evidence that the methionine substitution prevents the formation of the low-

SUBMITTER: Beattie NR 

PROVIDER: S-EPMC5293408 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature