Crystal Structure of the Complex of Brugia malayi Cyclophilin and Cyclosporin A † , ‡

Stanford Synchrotron Radiation Laboratory, SLAC, P.O. Box 4249, Bin 69, Stanford University, Stanford, California 94309, USA.
Biochemistry (Impact Factor: 3.02). 02/2000; 39(3):592-8. DOI: 10.1021/bi991730q
Source: PubMed


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 A. 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 A in this region.

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