A conformation of cyclosporin A in aqueous environment revealed by the X-ray structure of a cyclosporin-Fab complex.
The conformation of the immunosuppressive drug cyclosporin A (CsA) in a complex with a Fab molecule has been established by crystallographic analysis to 2.65 angstrom resolution. This conformation of CsA is similar to that recently observed in the complex with the rotamase cyclophilin, its binding protein in vivo, and totally different from its conformation in an isolated form as determined from x-ray and nuclear magnetic resonance analysis. Because the surfaces of CsA interacting with cyclophilin or with the Fab are not identical, these results suggest that the conformation of CsA observed in the bound form preexists in aqueous solution and is not produced by interaction with the proteins.
Altschuh
D
D
Vix
O
O
Rees
B
B
Thierry
J C
JC
D000591:Amino Acid Isomerases / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D016572:Cyclosporine / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019696:Peptidylprolyl Isomerase; D011485:Protein Binding; D011487:Protein Conformation; D012996:Solutions; D014961:X-Ray Diffraction / Q000379:methods
D002352:Carrier Proteins; D007140:Immunoglobulin Fab Fragments; D012996:Solutions; D016572:Cyclosporine; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase