Comparison of conformations of cyclosporin A and macrolide FK506 fragments: localization of putative binding sites with phosphatase calcineurin.
The three-dimensional structures of two immunosuppressants, cyclosporin A and macrolide FK506, were compared. The sites N-methylglycine3-N-methylleucine4 and valine5-N-methylleucine6 of cyclosporin A were found to be similar to each other (the root-mean-square value was 0.29 A for six reference points of the main chain) and also to the site C17-C22 of FK506 (the root-mean-square values were 0.33 A and 0.13 A, respectively). We suggest these fragments of cyclosporin A and FK506 make a major contribution to the interaction of the immunosuppressants with the phosphatase calcineurin.
Denesyuk
A I
AI
Institute of Immunology, Lyubuchany, Russia.
Korpela
T
T
Lundell
J
J
Sara
R
R
Zav'yalov
V P
VP
D000595:Amino Acid Sequence; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D016572:Cyclosporine / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011487:Protein Conformation; D016559:Tacrolimus / Q000737:chemistry* / Q000378:metabolism
D002148:Calmodulin-Binding Proteins; D010446:Peptide Fragments; D016572:Cyclosporine; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D016559:Tacrolimus