title: OMP decarboxylase: phosphodianion binding energy is used to stabilize a vinyl carbanion intermediate.
abstract: Orotidine 5'-monophosphate decarboxylase (OMPDC) catalyzes the exchange for deuterium from solvent D(2)O 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 × 10(4)-fold by 1 M phosphite dianion (HPO(3)(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 HPO(3)(2-). 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.
authors.affiliation: Department of Chemistry, University at Buffalo, Buffalo, New York 14260, USA.
authors.forename: Bogdana
authors.initials: B
authors.lastname: Goryanova
authors.forename: Tina L
authors.initials: TL
authors.lastname: Amyes
authors.forename: John A
authors.initials: JA
authors.lastname: Gerlt
authors.forename: John P
authors.initials: JP
authors.lastname: Richard
mesh_terms: D003903:Deuterium / Q000378:metabolism*; D005472:Fluorouracil / Q000378:metabolism; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000378:metabolism*; D017905:Phosphites / Q000378:metabolism*; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D013379:Substrate Specificity; D013816:Thermodynamics
chemical_list: D017905:Phosphites; D003903:Deuterium; D009964:Orotidine-5'-Phosphate Decarboxylase; D005472:Fluorouracil