A large-scale processing of kinetic data files with derivation of the inhibitory constant Ki: an application to proline isomerases.
An integral system of algorithms (file preprocessor + the adapted KORE program + the Powell non-linear least-squares minimizer) named KINMIN is described. This system was applied to simultaneously process a large number of kinetic data files for cis/trans isomerization of Xaa-Pro bonds in synthetic peptides catalysed by peptidylproline cis/trans isomerases which can be inhibited by nanomolar concentrations of the immunosuppressive compounds cyclosplorin-A, FK506 or rapamycin. The system allows preprocessing of kinetics data files and derives from them the first-order rate constants which are used to optimize the inhibitory constant Ki of each inhibitor. The KINMIN program may be also applied to derive Ki for other sets of enzymes and their inhibitors.
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Département d'Ingénierie et d'Etudes des Protéines (DIEP), CEA, Gif-sur-Yvette, France.
D000465:Algorithms; D000591:Amino Acid Isomerases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry; D019696:Peptidylprolyl Isomerase; D011090:Polyenes / Q000494:pharmacology; D020123:Sirolimus; D012984:Software; D013237:Stereoisomerism; D013379:Substrate Specificity; D016559:Tacrolimus / Q000494:pharmacology
D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D010455:Peptides; D011090:Polyenes; D016572:Cyclosporine; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase; D020123:Sirolimus; D016559:Tacrolimus