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 Alan 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

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Decarboxylation
Carboxy-Lyases
Stabilization
Orotic Acid
Phosphites
Substrates
Rate constants
Catalyst activity
Proteins
Substitution reactions
Chemical activation
Mutation
Enzymes
orotidylic acid

ASJC Scopus subject areas

  • Biochemistry

Cite this

Orotidine 5′-monophosphate decarboxylase : Transition state stabilization from remote protein-phosphodianion interactions. / Amyes, Tina L.; Ming, Shonoi A.; Goldman, Lawrence M.; Wood, B. McKay; Desai, Bijoy J.; Gerlt, John Alan; Richard, John P.

In: Biochemistry, Vol. 51, No. 23, 12.06.2012, p. 4630-4632.

Research output: Contribution to journalArticle

Amyes, Tina L. ; Ming, Shonoi A. ; Goldman, Lawrence M. ; Wood, B. McKay ; Desai, Bijoy J. ; Gerlt, John Alan ; Richard, John P. / Orotidine 5′-monophosphate decarboxylase : Transition state stabilization from remote protein-phosphodianion interactions. In: Biochemistry. 2012 ; Vol. 51, No. 23. pp. 4630-4632.
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AU - Gerlt, John Alan

AU - Richard, John P.

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