Crystal structure of cyclophilin A complexed with substrate Ala-Pro suggests a solvent-assisted mechanism of cis-trans isomerization.
AUTOR(ES)
Ke, H
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=46292Documentos Relacionados
- Mechanism of cis-trans Isomerization of Unsaturated Fatty Acids in Pseudomonas putida
- The gene for cyclophilin (peptidyl-prolyl cis-trans isomerase) from Schizosaccharomyces pombe.
- Catalysis of cis/trans isomerization in native HIV-1 capsid by human cyclophilin A
- Peptidyl prolyl cis-trans isomerase activity of cyclophilin A in functional homo-oligomeric receptor expression
- Evidence for involvement of proline cis-trans isomerization in the slow unfolding reaction of RNase A.
