Conformational Differences of an Immunosuppressant Peptolide in a Single Crystal and in a Crystal Complex with Human Cyclophilin A.

Abstract The crystal structure of (Thr2, Leu5, d -Hiv8, Leu10)-cyclosporin (cyclic peptolide SDZ 214–103) has been determined as the unbound crystal form and as a complex with human cyclophilin A. This pair of structures provides an example of a significant difference in conformation between free and bound ligand in crystals. The conformation of the unbound form is unlike that of both free and bound conformations of cyclosporin A (with the amide bond between residues 3 and 4 in the cis conformation), while the bound conformation is similar to that of CsA bound to cyclophilin. The cyclophilin-bound conformations of both ligands are similar, though this involves a significantly different water...ligand hydrogen-bonding structure, which compensates for the chemical differences between the two ligands.