title: Orotidine 5'-monophosphate decarboxylase: transition state stabilization from remote protein-phosphodianion interactions.
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.
authors.affiliation: Department of Chemistry, University at Buffalo, Buffalo, NY 14260, USA.
authors.forename: Tina L
authors.initials: TL
authors.lastname: Amyes
authors.forename: Shonoi A
authors.initials: SA
authors.lastname: Ming
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Goldman
authors.forename: B McKay
authors.initials: BM
authors.lastname: Wood
authors.forename: Bijoy J
authors.initials: BJ
authors.lastname: Desai
authors.forename: John A
authors.initials: JA
authors.lastname: Gerlt
authors.forename: John P
authors.initials: JP
authors.lastname: Richard
mesh_terms: D000838:Anions / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D015966:Gene Expression Regulation, Fungal; D007700:Kinetics; D008958:Models, Molecular; D009154:Mutation; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000737:chemistry* / Q000378:metabolism*; D017905:Phosphites / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D013379:Substrate Specificity; D015003:Yeasts / Q000201:enzymology
chemical_list: D000838:Anions; D017905:Phosphites; D009964:Orotidine-5'-Phosphate Decarboxylase