[6] Kinetics of slow and tight-binding inhibitors

作者: Stefan E. Szedlacsek , Ronald G. Duggleby

DOI: 10.1016/0076-6879(95)49034-5

关键词: Computational chemistryData interpretationMechanism (philosophy)Transition state analogSlow bindingTight bindingKineticsKinetic equationsChemistryReaction intermediate

摘要: Publisher Summary The interest in both slow and tight-binding inhibitors has been increasing, mainly, owing to their importance as chemotherapeutic agents, herbicides, transition state analogs (reaction intermediate analogs). Although the quantitative description of effects these poses special problems, it is worth emphasizing that there nothing intrinsically different between classical inhibitors. Usually, derivation kinetic equations for nonclassical carried out following way: first, an inhibition mechanism proposed; second, some simplifying assumptions are set up; and, third, corresponding deduced. On other hand, when constants a new (slow and/or tight-binding) inhibitor be determined, procedure used: one or two alternative mechanisms considered; fitted experimental data; finally, model giving best fit accepted correct taken real values. There extensive reviews about this type inhibition, which include aspects: review by Williams Morrison Walsh binding Thus, present chapter discusses aspects have received less attention well developments, concerning kinetics more general mechanism, validity commonly used assumptions, determine constants, recent models analysis inhibition.

参考文章(27)
Ian A. Nimmo, Gordon L. Atkins, A comparison of two methods for fitting the integrated Michaelis–Menten equation Biochemical Journal. ,vol. 141, pp. 913- 914 ,(1974) , 10.1042/BJ1410913
S E Szedlacsek, V Ostafe, R G Duggleby, M Serban, M O Vlad, Progress-curve equations for reversible enzyme-catalysed reactions inhibited by tight-binding inhibitors. Biochemical Journal. ,vol. 265, pp. 647- 653 ,(1990) , 10.1042/BJ2650647
Sungman Cha, Tight-binding inhibitors—III Biochemical Pharmacology. ,vol. 25, pp. 2695- 2702 ,(1976) , 10.1016/0006-2952(76)90259-8
C Erneux, S Cohen, D L Garbers, The kinetics of tyrosine phosphorylation by the purified epidermal growth factor receptor kinase of A-431 cells. Journal of Biological Chemistry. ,vol. 258, pp. 4137- 4142 ,(1983) , 10.1016/S0021-9258(18)32595-X
A Baici, Graphical and statistical analysis of hyperbolic tight-binding inhibition Biochemical Journal. ,vol. 244, pp. 793- 796 ,(1987) , 10.1042/BJ2440793
Alan Fersht, Enzyme structure and mechanism ,(1977)
Jeffrey W. Williams, John F. Morrison, Ronald G. Duggleby, Methotrexate, a high-affinity pseudosubstrate of dihydrofolate reductase. Biochemistry. ,vol. 18, pp. 2567- 2573 ,(1979) , 10.1021/BI00579A021
Jeffrey W. Williams, Ronald G. Duggleby, Robert Cutler, John F. Morrison, The inhibition of dihydrofolate reductase by folate analogues: structural requirements for slow- and tight-binding inhibition. Biochemical Pharmacology. ,vol. 29, pp. 589- 595 ,(1980) , 10.1016/0006-2952(80)90381-0
Klaus-Heinrich Röhm, Butylmalonate is a transition state analogue for aminocylase I FEBS Letters. ,vol. 250, pp. 191- 194 ,(1989) , 10.1016/0014-5793(89)80718-5