Enzyme architecture: the activating oxydianion binding domain for orotidine 5'-monophophate decarboxylase.

Orotidine 5'-monophosphate decarboxylase catalyzes the decarboxylation of truncated substrate (1-β-D-erythrofuranosyl)orotic acid to form (1-β-D-erythrofuranosyl)uracil. This enzyme-catalyzed reaction is activated by tetrahedral oxydianions, which bind weakly to unliganded OMPDC and tightly to the enzyme-transition state complex, with the following intrinsic oxydianion binding energies (kcal/mol): SO3(2-), -8.3; HPO3(2-), -7.7; S2O3(2-), -4.6; SO4(2-), -4.5; HOPO3(2-), -3.0; HOAsO3(2-), no activation detected. We propose that the oxydianion and orotate binding domains of OMPDC perform complementary functions in catalysis of decarboxylation reactions: (1) The orotate binding domain carries out decarboxylation of the orotate ring. (2) The activating oxydianion binding domain has the cryptic function of utilizing binding interactions with tetrahedral inorganic oxydianions to drive an enzyme conformational change that results in the stabilization of transition states at the distant orotate domain.