Mechanistic studies of peptidyl prolyl cis-trans isomerase: evidence for catalysis by distortion
- 20 February 1990
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 29 (7) , 1684-1689
- https://doi.org/10.1021/bi00459a003
Abstract
Cyclophilin, the cytosolic binding protein for the immunosuppressive drug cyclosporin A, has recently been shown to be identical with peptidyl prolyl cis-trans isomerase [Fischer, G., Wittmann-Liebold, B., Lang, K., Kiefhaber, T., and Schmid, F. X. (1989)Nature 337, 476; Takahashi, N., Hayano, T., and Suzuki, M. (1989) Nature 337, 473]. To provide a mechanistic framework for studies of the interaction of cyclophilin with cyclosporin, we investigated the mechanism of the PPI-catalyzed cis to trans isomerization of Suc-Ala-Xaa-cis-Pro-Phe-pNA (Xaa = Ala, Gly). Our mechanistic studies of peptidyl prolyl cis-trans isomerase include the determination of steady-state kinetic parameters, pH and temperature dependencies, and solvent and secondary deuterium isotope effects. The results of these experiments support a mechanism involving catalysis by distortion in which the enzyme uses free energy released from favorable, noncovalent interactions with the substrate to stabilize a transition state that is characterized by partial rotation about the C-N amide bond.This publication has 9 references indexed in Scilit:
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