Cyclosporin A-cyclophilin complex formation A model based on X-ray and NMR data

Claus Spitzfaden, Hans Peter Weber, Werner Braun, Joerg Kallen, Gerhard Wider, Hans Widmer, Malcolm D. Walkinshaw, Kurt Wüthrich

Research output: Contribution to journalArticlepeer-review

104 Scopus citations


The previously determined 3D NMR solution structure of cyclophilin-bound cyclosporin A (CsA) was docked onto the X-ray crystal structure of cyclophilin. Intermolecular nuclear Overhauser effects (NOE) between CsA and cyclophilin were used as constraints in a restrained energy minimization to generate a model of the complex which satisfied all the NOE distance constraints. The model shows that the residues 9 to 11 and 1 to 5 of the cyclic CsA molecule are in contact with cyclophilin. Comparing the model of the CsA-cyclophilin complex to the X-ray crystal structure of a complex of cyclophilin with a substrate for peptidyl-proline cis-trans isomerase activity, i.e. the linear tetrapeptide substrate ae-Ala-Ala-Pro-Ala-amc (ac. acetyl; amc. amidomethylcoumarin), one notices that the contacting peptide segments in the two ligands are oriented in opposite directions, and that the side chain or MeVal-11 of CsA superposes rather precisely with the position of the prolyl residue in ae-Ala-Ala-Pro-Ala-amc.

Original languageEnglish (US)
Pages (from-to)291-300
Number of pages10
JournalFEBS Letters
Issue number3
StatePublished - Apr 6 1992
Externally publishedYes


  • Complex formation
  • Cyclophilin
  • Cyclosporin A
  • NMR structure

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology


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