OMP decarboxylase

Phosphodianion binding energy is used to stabilize a vinyl carbanion intermediate

Bogdana Goryanova, Tina L. Amyes, John Alan Gerlt, John P. Richard

Research output: Contribution to journalArticle

Abstract

Orotidine 5′-monophosphate decarboxylase (OMPDC) catalyzes the exchange for deuterium from solvent D2O of the C-6 proton of 1-(β-d-erythrofuranosyl)-5-fluorouracil (FEU), a phosphodianion truncated product analog. The deuterium exchange reaction of FEU is accelerated 1.8 × 104-fold by 1 M phosphite dianion (HPO3 2-). This corresponds to a 5.8 kcal/mol stabilization of the vinyl carbanion-like transition state, which is similar to the 7.8 kcal/mol stabilization of the transition state for OMPDC-catalyzed decarboxylation of a truncated substrate analog by bound HPO32-. These results show that the intrinsic binding energy of phosphite dianion is used in the stabilization of the vinyl carbanion-like transition state common to the decarboxylation and deuterium exchange reactions.

Original languageEnglish (US)
Pages (from-to)6545-6548
Number of pages4
JournalJournal of the American Chemical Society
Volume133
Issue number17
DOIs
StatePublished - May 4 2011

Fingerprint

Orotidine-5'-Phosphate Decarboxylase
Deuterium
deuterium
Binding energy
Phosphites
decarboxylation
stabilization
Decarboxylation
Carboxy-Lyases
Stabilization
energy
Fluorouracil
Protons
fold
substrate
Substrates
orotidylic acid

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

OMP decarboxylase : Phosphodianion binding energy is used to stabilize a vinyl carbanion intermediate. / Goryanova, Bogdana; Amyes, Tina L.; Gerlt, John Alan; Richard, John P.

In: Journal of the American Chemical Society, Vol. 133, No. 17, 04.05.2011, p. 6545-6548.

Research output: Contribution to journalArticle

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N2 - Orotidine 5′-monophosphate decarboxylase (OMPDC) catalyzes the exchange for deuterium from solvent D2O of the C-6 proton of 1-(β-d-erythrofuranosyl)-5-fluorouracil (FEU), a phosphodianion truncated product analog. The deuterium exchange reaction of FEU is accelerated 1.8 × 104-fold by 1 M phosphite dianion (HPO3 2-). This corresponds to a 5.8 kcal/mol stabilization of the vinyl carbanion-like transition state, which is similar to the 7.8 kcal/mol stabilization of the transition state for OMPDC-catalyzed decarboxylation of a truncated substrate analog by bound HPO32-. These results show that the intrinsic binding energy of phosphite dianion is used in the stabilization of the vinyl carbanion-like transition state common to the decarboxylation and deuterium exchange reactions.

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