Analogous conformations of both binding and effector regions in cyclosporin A, FK506 and rapamycin

Comput Chem. 1998 Jun 20;22(4):339-44. doi: 10.1016/s0097-8485(97)00067-3.

Abstract

Three immunosuppressant drugs, cyclosporin A, FK506 and rapamycin were compared in their three-dimensional structures by computer modelling. The pairwise comparisons of cyclosporin A, FK506 and rapamycin show two structurally common fragments. One fragment is Mle9-Bmt1 region in cyclosporin A, C22-O5 region in FK506 and C29-O5 region in rapamycin. Another fragment is Mle4-Mle6 region in cyclosporin A and C14-C21 regions in FK506 and rapamycin. The correspondence of the structurally analogous regions with the regions which are involved in the interactions with peptidyl-prolyl cis/trans isomerases and calcineurin or FKBP-rapamycin-associated protein is discussed.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Binding Sites
  • Calcineurin / metabolism
  • Carrier Proteins / metabolism
  • Computer Simulation
  • Cyclosporine / chemistry*
  • Cyclosporine / metabolism
  • Immunophilins*
  • Immunosuppressive Agents / chemistry*
  • Immunosuppressive Agents / metabolism
  • Models, Molecular
  • Peptidylprolyl Isomerase / metabolism
  • Polyenes / chemistry*
  • Polyenes / metabolism
  • Sirolimus
  • Tacrolimus / chemistry*
  • Tacrolimus / metabolism

Substances

  • Carrier Proteins
  • Immunosuppressive Agents
  • Polyenes
  • Cyclosporine
  • Calcineurin
  • Immunophilins
  • Peptidylprolyl Isomerase
  • Sirolimus
  • Tacrolimus