Analogous conformations of both binding and effector regions in cyclosporin A, FK506 and rapamycin.
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.
Institute of Immunological Engineering, Moscow Region, Russia.
A I
AI
Denesyuk
K A
KA
Denessiouk
V P
VP
Zav'yalov
J
J
Lundell
T
T
Korpela
D001665:Binding Sites; D019703:Calcineurin / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D003198:Computer Simulation; D016572:Cyclosporine / Q000737:chemistry* / Q000378:metabolism; D020104:Immunophilins; D007166:Immunosuppressive Agents / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D019696:Peptidylprolyl Isomerase / Q000378:metabolism; D011090:Polyenes / Q000737:chemistry* / Q000378:metabolism; D020123:Sirolimus; D016559:Tacrolimus / Q000737:chemistry* / Q000378:metabolism
D002352:Carrier Proteins; D007166:Immunosuppressive Agents; D011090:Polyenes; D016572:Cyclosporine; D019703:Calcineurin; D020104:Immunophilins; D019696:Peptidylprolyl Isomerase; D020123:Sirolimus; D016559:Tacrolimus