1CYA

NMR STUDIES OF (U-13C)CYCLOSPORIN A BOUND TO CYCLOPHILIN: BOUND CONFORMATION AND PORTIONS OF CYCLOSPORIN INVOLVED IN BINDING

Summary for 1CYA

• Entry DOI: 10.2210/pdb1cya/pdb
• Related: 1BCK 1C5F 1CSA 1CWA 1CWB 1CWC 1CWF 1CWH 1CWI 1CWJ 1CWK 1CWL 1CWM 1CWO 1CYB 1CYN 1IKF 1M63 1MF8 1MIK 1QNG 1QNH 1XQ7 2ESL 2OJU 2POY 2RMA 2RMB 2RMC 2WFJ 2X2C 2X7K 2Z6W 3BO7 3CYS 3EOV
• Related PRD ID: PRD_000142
• Descriptor: CYCLOSPORIN A (1 entity in total)
• Functional Keywords: immunosuppressant, cyclosporin a
• Biological source: TOLYPOCLADIUM INFLATUM
• Total number of polymer chains: 1
• Total formula weight: 1220.63

Authors

Fesik, S.W. (deposition date: 1992-02-24, release date: 1994-01-31, Last modification date: 2024-06-05)

Primary citation

Fesik, S.W.,Gampe, R.T.,Eaton, H.L.,Gemmecker, G.,Olejniczak, E.T.,Neri, P.,Holzman, T.F.,Egan, D.A.,Edalji, R.
NMR Studies of [U-13C]Cyclosporin a Bound to Cyclophilin: Bound Conformation and Portions of Cyclosporin Involved in Binding.
Biochemistry, 30:6574-, 1991

PubMed Abstract: Cyclosporin A (CsA), a potent immunosuppressant, is known to bind with high specificity to cyclophilin (CyP), a 17.7 kDa protein with peptidyl-prolyl isomerase activity. In order to investigate the three-dimensional structure of the CsA/CyP complex, we have applied a variety of multidimensional NMR methods in the study of uniformly 13C-labeled CsA bound to cyclophilin. The 1H and 13C NMR signals of cyclosporin A in the bound state have been assigned, and from a quantitative interpretation of the 3D NOE data, the bound conformation of CsA has been determined. Three-dimensional structures of CsA calculated from the NOE data by using a distance geometry/simulated appealing protocol were found to be very different from previously determined crystalline and solution conformations of uncomplexed CsA. In addition, from CsA/CyP NOEs, the portions of CsA that interact with cyclophilin were identified. For the most part, those CsA residues with NOEs to cyclophilin were the same residues important for cyclophilin binding and immunosuppressive activity as determined from structure/activity relationships. The structural information derived in this study together with the known structure/activity relationships for CsA analogues may prove useful in the design of improved immunosuppressants. Moreover, the approach that is described for obtaining the structural information is widely applicable to the study of small molecule/large molecule interactions.

PubMed: 2054356
DOI: 10.1021/BI00240A030

Experimental method

SOLUTION NMR