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Transition state structure of Salmonella typhimurium orotate phosphoribosyltransferase.
Biochemistry. 1996 Jan 09; 35(1):14-21.B

Abstract

Orotate phosphoribosyltransferase (OPRTase) catalyzes the magnesium-dependent conversion of alpha-D-phosphoribosylpyrophosphate (PRPP) and orotate to orotidine 5'-monophosphate (OMP) and pyrophosphate. We have determined kinetic isotope effects on the reaction of OMP with pyrophosphate and with the pyrophosphate analog phosphonoacetic acid. In the latter case, full expression of the kinetic isotope effects allowed us to calculate the structure of the transition state for the pyrophosphorylytic reaction. The transition state resembles a classical oxocarbonium ion. Using the recently reported three-dimensional structures of the OPRTase-OMP (Scapin et al., 1994) and the OPRTase-PRPP complexes (Scapin et al., 1995a), we have modeled the calculated transition state structure into the active site of OPRTase. We propose a detailed chemical mechanism which is consistent with these results.

Authors+Show Affiliations

Tao W
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Grubmeyer C
No affiliation info available
Blanchard JS
No affiliation info available

MeSH

Carbon RadioisotopesDiphosphatesHydrogen BondingIsotope LabelingKineticsModels, MolecularMolecular ConformationOrotate PhosphoribosyltransferaseProtein Structure, SecondarySalmonella typhimuriumTritiumUridine Monophosphate

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8555167

Citation

Tao, W, et al. "Transition State Structure of Salmonella Typhimurium Orotate Phosphoribosyltransferase." Biochemistry, vol. 35, no. 1, 1996, pp. 14-21.
Tao W, Grubmeyer C, Blanchard JS. Transition state structure of Salmonella typhimurium orotate phosphoribosyltransferase. Biochemistry. 1996;35(1):14-21.
Tao, W., Grubmeyer, C., & Blanchard, J. S. (1996). Transition state structure of Salmonella typhimurium orotate phosphoribosyltransferase. Biochemistry, 35(1), 14-21.
Tao W, Grubmeyer C, Blanchard JS. Transition State Structure of Salmonella Typhimurium Orotate Phosphoribosyltransferase. Biochemistry. 1996 Jan 9;35(1):14-21. PubMed PMID: 8555167.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transition state structure of Salmonella typhimurium orotate phosphoribosyltransferase. AU - Tao,W, AU - Grubmeyer,C, AU - Blanchard,J S, PY - 1996/1/9/pubmed PY - 1996/1/9/medline PY - 1996/1/9/entrez SP - 14 EP - 21 JF - Biochemistry JO - Biochemistry VL - 35 IS - 1 N2 - Orotate phosphoribosyltransferase (OPRTase) catalyzes the magnesium-dependent conversion of alpha-D-phosphoribosylpyrophosphate (PRPP) and orotate to orotidine 5'-monophosphate (OMP) and pyrophosphate. We have determined kinetic isotope effects on the reaction of OMP with pyrophosphate and with the pyrophosphate analog phosphonoacetic acid. In the latter case, full expression of the kinetic isotope effects allowed us to calculate the structure of the transition state for the pyrophosphorylytic reaction. The transition state resembles a classical oxocarbonium ion. Using the recently reported three-dimensional structures of the OPRTase-OMP (Scapin et al., 1994) and the OPRTase-PRPP complexes (Scapin et al., 1995a), we have modeled the calculated transition state structure into the active site of OPRTase. We propose a detailed chemical mechanism which is consistent with these results. SN - 0006-2960 UR - https://www.unboundmedicine.com/medline/citation/8555167/Transition_state_structure_of_Salmonella_typhimurium_orotate_phosphoribosyltransferase_ L2 - https://doi.org/10.1021/bi951898l DB - PRIME DP - Unbound Medicine ER -