Conformational differences of an immunosuppressant peptolide in a single crystal and in a crystal complex with human cyclophilin A.
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 waterellipsisligand hydrogen-bonding structure, which compensates for the chemical differences between the two ligands.
The University of Edinburgh, Michael Swann Building, Edinburgh, EH9 3JR, UK.
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Taylor
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Walkinshaw
D003524:Cyclosporins / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D020104:Immunophilins / Q000737:chemistry; D007166:Immunosuppressive Agents / Q000737:chemistry* / Q000494:pharmacology; D046911:Macromolecular Substances; D008958:Models, Molecular; D019696:Peptidylprolyl Isomerase / Q000737:chemistry*; D011487:Protein Conformation; D014961:X-Ray Diffraction
D003524:Cyclosporins; D007166:Immunosuppressive Agents; D046911:Macromolecular Substances; C115470:peptolide 214103; D020104:Immunophilins; D019696:Peptidylprolyl Isomerase