Crystal structure of the complex of brugia malayi cyclophilin and cyclosporin A.
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.
Ellis
P J
PJ
Stanford Synchrotron Radiation Laboratory, SLAC, P.O. Box 4249, Bin 69, Stanford University, Stanford, California 94309, USA.
Carlow
C K
CK
Ma
D
D
Kuhn
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017178:Brugia malayi / Q000201:enzymology* / Q000235:genetics; D018360:Crystallography, X-Ray / Q000379:methods; D016572:Cyclosporine / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D019696:Peptidylprolyl Isomerase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
D011994:Recombinant Proteins; D016572:Cyclosporine; D019696:Peptidylprolyl Isomerase