Kinetic β‐deuterium isotope effects suggest a covalent mechanism for the protein folding enzyme peptidylprolyl cis/trans‐isomerase
- 3 July 1989
- journal article
- Published by Wiley in FEBS Letters
- Vol. 250 (2), 267-270
- https://doi.org/10.1016/0014-5793(89)80735-5
Abstract
The cis/trans interconversion of Glt-Ala-Ala-Pro-Phe-4-nitroanilide and Glt-Ala-Gly-Pro-Phe-4-nitroanilide was studied both enzymatically and nonenzymatically by measuring kinetic β-deuterium isotope effects. The hydrogen atom at the α-carbon atom of the Xaa residue within the Xaa-Pro moiety was substituted by deuterium. In the nonenzymatic case the transition state of rotation is reflected by kH/kD > 1. When catalysed by 17 kDa PPIase the same bond rotation is characterized by kH/kD < 1. This suggests a covalent mechanism of catalysis which involves an approximately tetravalent carbon of the prolyl imidic bond for the transition state of reactionThis publication has 18 references indexed in Scilit:
- Folding of immunogenic peptide fragments of proteins in water solution: I. Sequence requirements for the formation of a reverse turnJournal of Molecular Biology, 1988
- Protein-disulphide isomerase and prolyl isomerase act differently and independently as catalysts of protein foldingNature, 1988
- Isomer-specific proteolysis of model substrates: influence that the location of the proline residue exerts on cis trans specificityBiochemistry, 1985
- The refolding of urea-denatured ribonuclease A is catalyzed by peptidyl-prolyl cis-trans isomeraseBiochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1985
- Réactions d'addition nucléophile sur les cétones dépendence conformationnelle de l'effet isotopiqueRecueil des Travaux Chimiques des Pays-Bas, 1985
- Conformational specificity of chymotrypsin toward proline-containing substratesBiochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1984
- Transition-state structural features for anilide hydrolysis from .beta.-deuterium isotope effectsJournal of the American Chemical Society, 1984
- Use of Isotope Effects to Elucidate Enzyme MechanismCritical Reviews in Biochemistry, 1982
- The .beta.-hydrogen secondary isotope effect in acyl transfer reactions. Origins, temperature dependence, and utility as a probe of transition-state structureJournal of the American Chemical Society, 1980
- On the conformational dependence of secondary .beta.-deuterium isotope effectsJournal of the American Chemical Society, 1979