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Mechanistic implication of crystal structures of the cyclophilin-dipeptide complexes.

Zhao Y, Ke H
Biochemistry 35 7362-8 (1996)
Related entries: 2cyh, 3cyh, 5cyh

Cited: 37 times
EuropePMC logo PMID: 8652512

Abstract

The structures of cyclophilin A complexed with dipeptides of Ser-Pro, His-Pro, and Gly-Pro have been determined and refined at high resolution. Comparison of these structures revealed that the dipeptide complexes have the same molecular conformation and the same binding of the dipeptides. The side chains of the N-terminal amino acid of the above dipeptides do not strongly interact with cyclophilin, implying their minor contribution to the cis-trans isomerization and thus accounting for the broad catalytic specificity of the enzyme. The binding of the dipeptides is similar to that of the common substrate succinyl-Ala-Ala-Pro-Phe-p-nitroanilide in terms of the N-terminal hydrogen bonding and the hydrophobic interaction of the proline side chain. However, substantial difference between these structures are observed in (1) hydrogen bonding between the carboxyl terminus of the peptides and Arg55 and between Arg55 and Gln63, (2) the side chain conformation of Arg55, and (3) water binding at the active site. These differences imply either that dipeptides are not substrates but competitive inhibitors of peptidyl-prolyl cis-trans isomerases or that dipeptides are subject to different catalytic mechanisms from tetrapeptides.

Reviews citing this publication (2)

  1. Immunophilins: switched on protein binding domains? Ivery MT. Med Res Rev 20 452-484 (2000)
  2. Peptidyl-prolyl isomerase inhibitors. Wang XJ, Etzkorn FA. Biopolymers 84 125-146 (2006)

Articles citing this publication (35)

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