Isoform-Specific Inhibition of Cyclophilins

被引：60

作者：

Daum, Sebastian ^{[1
]}

Schumann, Michael ^{[1
]}

Mathea, Sebastian ^{[1
]}

Aumueller, Tobias ^{[1
]}

Balsley, Molly A. ^{[2
]}

Constant, Stephanie L. ^{[2
]}

de Lacroix, Boris Feaux ^{[3
]}

Kruska, Fabian ^{[3
]}

Braun, Manfred ^{[3
]}

Schiene-Fischer, Cordelia ^{[1
]}

机构：

[1] Max Planck Res Unit Enzymol Prot Folding, D-06120 Halle, Germany

[2] George Washington Univ, Dept Microbiol Immunol & Trop Med, Washington, DC 20037 USA

[3] Univ Dusseldorf, Dept Chem, D-40225 Dusseldorf, Germany

来源：

BIOCHEMISTRY | 2009年 / 48卷 / 26期

基金：

美国国家卫生研究院;

关键词：

HEPATITIS-C-VIRUS; PROTEIN EXPRESSION PROFILES; PEPTIDYL-PROLYL ISOMERASE; CIS-TRANS ISOMERASE; CYCLOSPORINE-A; BINDING; REPLICATION; MITOCHONDRIAL; AFFINITY; LIGAND;

D O I：

10.1021/bi9007287

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：

Cyclophilins belong to the enzyme class of peptidyl prolyl cis-trans isomerases which catalyze the cis-trans isomerization of prolyl bonds in peptides and proteins in different folding states. Cyclophilins have been shown to be involved in a multitude of cellular functions like cell growth, proliferation, and motility. Among the 20 human cyclophilin isoenzymes, the two most abundant members of the cyclophilin family, CypA and CypB, exhibit specific cellular functions in several inflammatory diseases, cancer development, and HCV replication. A small-molecule inhibitor on the basis of aryl l-indanylketones has now been shown to discriminate between CypA and CypB in vitro. CypA binding of this inhibitor has been characterized by fluorescence anisotropy- and isothermal titration calorimetry-based cyclosporin competition assays. Inhibition of CypA- but not CypB-mediated chemotaxis of mouse CD4(+) T cells by the inhibitor provided biological proof of discrimination in vivo.

引用

页码：6268 / 6277

页数：10

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