Orotidine 5′-monophosphate decarboxylase: Transition state stabilization from remote protein-phosphodianion interactions

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)4630-4632
Number of pages3
JournalBiochemistry
Volume51
Issue number23
DOIs
StatePublished - Jun 12 2012

ASJC Scopus subject areas

  • Biochemistry

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    Amyes, T. L., Ming, S. A., Goldman, L. M., Wood, B. M. K., Desai, B. J., Gerlt, J. A., & Richard, J. P. (2012). Orotidine 5′-monophosphate decarboxylase: Transition state stabilization from remote protein-phosphodianion interactions. Biochemistry, 51(23), 4630-4632. https://doi.org/10.1021/bi300585e