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 journalArticle

97 Citations (Scopus)

Abstract

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
Volume300
Issue number3
DOIs
StatePublished - Apr 6 1992
Externally publishedYes

Fingerprint

Cyclophilins
Cyclosporine
Nuclear magnetic resonance
X-Rays
X rays
cis-trans-Isomerases
Crystal structure
Peptidylprolyl Isomerase
Substrates
Proline
Ligands
Peptides
Molecules

Keywords

  • Complex formation
  • Cyclophilin
  • Cyclosporin A
  • NMR structure

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Spitzfaden, C., Weber, H. P., Braun, W., Kallen, J., Wider, G., Widmer, H., ... Wüthrich, K. (1992). Cyclosporin A-cyclophilin complex formation A model based on X-ray and NMR data. FEBS Letters, 300(3), 291-300. https://doi.org/10.1016/0014-5793(92)80866-F

Cyclosporin A-cyclophilin complex formation A model based on X-ray and NMR data. / Spitzfaden, Claus; Weber, Hans Peter; Braun, Werner; Kallen, Joerg; Wider, Gerhard; Widmer, Hans; Walkinshaw, Malcolm D.; Wüthrich, Kurt.

In: FEBS Letters, Vol. 300, No. 3, 06.04.1992, p. 291-300.

Research output: Contribution to journalArticle

Spitzfaden, C, Weber, HP, Braun, W, Kallen, J, Wider, G, Widmer, H, Walkinshaw, MD & Wüthrich, K 1992, 'Cyclosporin A-cyclophilin complex formation A model based on X-ray and NMR data', FEBS Letters, vol. 300, no. 3, pp. 291-300. https://doi.org/10.1016/0014-5793(92)80866-F
Spitzfaden, Claus ; Weber, Hans Peter ; Braun, Werner ; Kallen, Joerg ; Wider, Gerhard ; Widmer, Hans ; Walkinshaw, Malcolm D. ; Wüthrich, Kurt. / Cyclosporin A-cyclophilin complex formation A model based on X-ray and NMR data. In: FEBS Letters. 1992 ; Vol. 300, No. 3. pp. 291-300.
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