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Interaction of human cyclophilin hCyp‐18 with short peptides suggests the existence of two functionally independent subsites
Author(s) -
Demange Luc,
Moutiez Mireille,
Vaudry Karine,
Dugave Christophe
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02814-9
Subject(s) - chemistry , stereochemistry , isomerase , cyclophilin , proline , peptide , biochemistry , enzyme , amino acid , gene
The binding of peptides, derived from the model substrate Suc‐Ala‐Ala‐Pro‐Phe‐pNA, to the human cyclophilin hCyp‐18 was investigated. HCyp‐18 is able to bind 2–4‐mer peptides as well as shorter para ‐nitroaniline (pNA) derivatives and pNA surrogates. Although Suc‐Ala‐Phe‐pNA binds hCyp‐18, only proline‐containing peptides are able to block efficiently the peptidyl‐prolyl cis/trans isomerase activity. Competition experiments strongly suggest the existence of two independent subsites: a S1′ ‘proline’ subsite and a S2′–S3′ ‘pNA’ subsite. The interaction at S2’–S3’ requires either a Phe‐pNA C‐terminus or a Phe‐pNA surrogate bearing an H‐bond acceptor able to bind Trp121 and Arg148 simultaneously.