Crystal structure of the complex of Brugia malayi cyclophilin and cyclosporin A

被引：8

作者：

Ellis, PJ

Carlow, CKS

Ma, D

Kuhn, P

机构：

[1] Stanford Univ, Stanford Linear Accelerator Ctr, Stanford Synchrotron Radiat Lab, Stanford, CA 94309 USA

[2] New England Biolabs Inc, Beverly, MA 01915 USA

来源：

BIOCHEMISTRY | 2000年 / 39卷 / 03期

关键词：

D O I：

10.1021/bi991730q

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 resistance of the human parasite Brugia malayi to the antiparasitic activity of cyclosporin A (CsA) may arise from the presence of cyclophilins with relatively low affinity for the drug. The structure of the complex of B. malayi cyclophilin (BmCYP-1) and CsA, with eight independent copies in the asymmetric unit, has been determined at a resolution of 2.7 Angstrom. The low affinity of BmCYP-1 for CsA arises from incomplete preorganization of the binding site so that the formation of a hydrogen bond between His132 of BmCYP-1 and N-methylleucine 9 of CsA is associated with a shift in the backbone of approximately 1 Angstrom in this region.

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页码：592 / 598

页数：7

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