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

The resistance of the human parasite Brugia malayi to the antiparasitic act ivity of cyclosporin A (CsA) may arise from the presence of cyclophilins wi th 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 t he 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 back bone of approximately 1 Angstrom in this region.