Interaction of human cyclophilin hCyp-18 with short peptides suggests the existence of two functionally independent subsites.
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.
Demange
L
L
CEA/Saclay, Département d'Ingénierie et d'Etudes des Protéines, Bâtiment 152, 91191 Gif-sur-Yvette, France.
Moutiez
M
M
Vaudry
K
K
Dugave
C
C
D021983:Cyclophilins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D019696:Peptidylprolyl Isomerase / Q000378:metabolism; D013329:Structure-Activity Relationship
D009842:Oligopeptides; D010455:Peptides; C437224:cyclophilin hCyp-18; C043307:succinyl-alanyl-alanyl-prolyl-phenylalanine-4-nitroanilide; D021983:Cyclophilins; D019696:Peptidylprolyl Isomerase