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

Tina L Amyes, Shonoi A Ming, Lawrence M Goldman, B McKay Wood, Bijoy J Desai, John A Gerlt, John P Richard

Biochemistry 2012 Jun 12

filter terms:

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.

Citation

Tina L Amyes, Shonoi A Ming, Lawrence M Goldman, B McKay Wood, Bijoy J Desai, John A Gerlt, John P Richard. Orotidine 5'-monophosphate decarboxylase: transition state stabilization from remote protein-phosphodianion interactions. Biochemistry. 2012 Jun 12;51(23):4630-2