Interaction of human cyclophilin hCyp-18 with short peptides suggests the existence of two functionally independent subsites

被引:16
作者
Demange, L [1 ]
Moutiez, M [1 ]
Vaudry, K [1 ]
Dugave, C [1 ]
机构
[1] CEA Saclay, Dept Ingn & Etud Prot, F-91191 Gif Sur Yvette, France
关键词
peptidyl-prolyl cis/trans isomerase; proline; cis/trans isomerization; subsite;
D O I
10.1016/S0014-5793(01)02814-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.
引用
收藏
页码:191 / 195
页数:5
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