Crystal structure implies that cyclophilin predominantly catalyzes the trans to cis isomerization.

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Citation

Zhao Y, Ke H

Crystal structure implies that cyclophilin predominantly catalyzes the trans to cis isomerization.

Biochemistry. 1996 Jun 11;35(23):7356-61.

PubMed ID
8652511 [ View in PubMed
]
Abstract

The crystal structure of human recombinant cyclophilin A complexed with a substrate of succinyl-Ala-Ala-Pro-Phe-p-nitroanilide (AAPF) has been determined and refined to an R-factor of 0.189 at 2.4 A resolution. The structure revealed only the cis form of the substrate bound to cyclophilin A in a stoichiometry of 1:1. This binding ratio is different from the structure of cyclophilin A complexed with the tetrapeptide N-acetyl-Ala-Ala-Pro-Ala-amidomethylcourmarin. Model docking revealed that the trans form of AAPF does not fit into the active site. The observation that only the trans cis form of AAPF binds to cyclophilin A implies that cyclophilin A predominantly catalyzes the trans to cis isomerization of a peptidylprolyl amide bond. On the basis of the structure, it is proposed that Arg55 hydrogen-bonds to the nitrogen to deconjugate the resonance of the prolyl amide bond and thus facilitates the cis-trans rotation.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Peptidyl-prolyl cis-trans isomerase AP62937Details