Journal article
Solution structure of the cyclosporin A/cyclophilin complex by NMR
Nature (London), Vol.361(6407), pp.88-91
01/07/1993
DOI: 10.1038/361088a0
PMID: 8421500
Abstract
Cyclosporin A, a cyclic undecapeptide, is a potent immuno-suppressant that binds to a peptidyl-prolyl isomeraseof 165 amino acids, cyclophilin The cyclosporin A/cyclophilin complex inhibits the calcium- and calmodulin-dependent phos-phatase, 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 cyclophilinhave 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 complexand is analysed in terms of the binding interactions and structure/activity relationships for CsA analogues
Details
- Title: Subtitle
- Solution structure of the cyclosporin A/cyclophilin complex by NMR
- Creators
- Yves Thériault - Discovery LaboratoriesTimothy M. Logan - Discovery LaboratoriesRobert Meadows - Discovery LaboratoriesLiping Yu - Discovery LaboratoriesEdward T. Olejniczak - AbbottThomas F. Holzman - AbbottRobert L. Simmer - Discovery LaboratoriesStephen W. Fesik - Discovery Laboratories
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.361(6407), pp.88-91
- DOI
- 10.1038/361088a0
- PMID
- 8421500
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Language
- English
- Date published
- 01/07/1993
- Academic Unit
- Biochemistry and Molecular Biology; Medicine Administration
- Record Identifier
- 9984627304802771
Metrics
4 Record Views