PDBsum entry 2cyh

Isomerase

PDB id: 2cyh

Contents

Protein chain

164 a.a. *

Ligands

ALA-PRO

Waters ×261

* Residue conservation analysis

References listed in PDB file

Key reference

• Title: Mechanistic implication of crystal structures of the cyclophilin-Dipeptide complexes.
• Authors: Y.Zhao, H.Ke.
• Ref.: Biochemistry, 1996, 35, 7362-7368. [DOI no: 10.1021/bi960278x]
• PubMed id: 8652512

Note In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above were identified by an automated search of PubMed on title and author names, giving a perfect match.

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.