Orotidine 5'-monophosphate decarboxylase: transition state stabilization from remote protein-phosphodianion interactions.

ABSTRACT: Mutants of orotidine 5'-monophosphate decarboxylase containing all possible single (Q215A, Y217F, and R235A), double, and triple substitutions of the side chains that interact with the phosphodianion group of the substrate orotidine 5'-monophosphate have been prepared. Essentially the entire effect of these mutations on the decarboxylation of the truncated neutral substrate 1-(β-d-erythrofuranosyl)orotic acid that lacks a phosphodianion group is expressed as a decrease in the third-order rate constant for activation by phosphite dianion. The results are consistent with a model in which phosphodianion binding interactions are utilized to stabilize a rare closed enzyme form that exhibits a high catalytic activity for decarboxylation.

SUBMITTER: Amyes TL 

PROVIDER: S-EPMC3431445 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature