Abstract：
:Cyclosporin A, a cyclic undecapeptide, is a potent immunosuppressant that binds to a peptidyl-prolyl cis-trans isomerase of 165 amino acids, cyclophilin. The cyclosporin A/cyclophilin complex inhibits the calcium- and calmodulin-dependent phosphatase, calcineurin, resulting in a failure to activate genes encoding interleukin-2 and other lymphokines. The three-dimensional structures of uncomplexed cyclophilin, a tetrapeptide/cyclophilin complex, and cyclosporin A when bound to cyclophilin have been reported. However, the structure of the cyclosporin A/cyclophilin complex has not been determined. Here we present the solution structure of the cyclosporin A/cyclophilin complex obtained by heteronuclear three-dimensional NMR spectroscopy. The structure, one of the largest determined by NMR, differs from proposed models of the complex and is analysed in terms of the binding interactions and structure/activity relationships for CsA analogues.
journal_name
Naturejournal_title
Natureauthors
Thériault Y,Logan TM,Meadows R,Yu L,Olejniczak ET,Holzman TF,Simmer RL,Fesik SWdoi
10.1038/361088a0subject
Has Abstractpub_date
1993-01-07 00:00:00pages
88-91issue
6407eissn
0028-0836issn
1476-4687journal_volume
361pub_type
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