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. 1993 Apr 15;90(8):3324–3328. doi: 10.1073/pnas.90.8.3324

Crystal structure of cyclophilin A complexed with substrate Ala-Pro suggests a solvent-assisted mechanism of cis-trans isomerization.

H Ke 1, D Mayrose 1, W Cao 1
PMCID: PMC46292  PMID: 8475075

Abstract

Cyclophilin is a binding protein for the immunosuppressive drug cyclosporin A and is also an enzyme with peptidyl-prolyl cis-trans isomerase activity. The crystal structure of cyclophilin A complexed with the substrate Ala-Pro has been determined and refined to an R factor of 0.196 at 1.64-A resolution. The structure shows that only the cis form of Ala-Pro binds cyclophilin A despite the fact that Ala-Pro has an equilibrium majority of the trans form in solution. Simulation of the cis-trans isomerization in an ESV10 graphics system suggests a solvent-assisted mechanism in which first the peptidyl-prolyl bond is desolvated at the ground state by binding to the hydrophobic pocket of the active site, and later the intermediate state is stabilized by a hydrogen bond between the carbonyl oxygen of the amide bond and a bound water molecule.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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