PMID: 8948491Nov 14, 1996Paper

Slow-binding inhibition: the general case

Biochimica Et Biophysica Acta
M J SculleyW W Cleland

Abstract

Two basic kinetic mechanisms have been described to account for the slow-binding inhibition of enzyme-catalyzed reactions. One mechanism involves the slow interaction of an inhibitor with enzyme (Mechanism A), while the other involves the rapid formation of an enzyme-inhibitor complex that undergoes a slow isomerization reaction (Mechanism B). But the initial interaction of enzyme and inhibitor may not necessarily be fast so that the free enzyme and the two forms of enzyme inhibitor complex are in steady-state equilibrium. This assumption would give rise to a more general form of Mechanism B. The present study has been concerned with attempts to determine whether it might be possible to distinguish between the three possible inhibition mechanisms by steady-state kinetic techniques. The approach to the investigation has been to derive theoretical data for the most general mechanism by using three different ratios for the two rate constants that determine which mechanism applies. The progress curve data were then fitted to the rate equations that describe the other two mechanisms. The results draw attention to the difficulties of deducing that experimental data conform to the most general mechanism. They also show how the values ...Continue Reading

References

Jan 1, 1979·Methods in Enzymology·W W Cleland

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Citations

May 12, 2004·Biochimica Et Biophysica Acta·David E EhmannStewart L Fisher
Jul 29, 2000·Physiology & Behavior·P KelliherB E Leonard
Sep 22, 2001·Biochimica Et Biophysica Acta·F ClemensP Frohberg
Oct 26, 1999·Bio Systems·C Garrido-del SoloR V Castellanos
Apr 3, 2010·Biochemistry·Alison L SikoraJohn S Blanchard
May 7, 2011·Biochemistry·Richard S HallFrank M Raushel
Jan 16, 2013·Journal of the American Chemical Society·Karnjapan JanthawornpongMyriam Seemann
Oct 1, 2008·Antimicrobial Agents and Chemotherapy·Scott D SeiwertLawrence M Blatt
Feb 14, 2016·Archives of Biochemistry and Biophysics·Patrick Masson, Sofya V Lushchekina
May 15, 2015·Journal of Medicinal Chemistry·Kevin B DanielSeth M Cohen
Jul 1, 2004·Biochemistry and Molecular Biology Education : a Bimonthly Publication of the International Union of Biochemistry and Molecular Biology·Marko Goliĉnik, Jure Stojan
Aug 11, 2015·The Journal of Physical Chemistry. B·Pascale R LeroueilMark M Banaszak Holl
Jan 13, 2010·Organic & Biomolecular Chemistry·Tracey M Gloster, Gideon J Davies
Aug 26, 2016·Journal of Enzyme Inhibition and Medicinal Chemistry·Xue Fei TanKi Hun Park
Jan 10, 2009·Journal of the American Chemical Society·Marko GolicnikFlorian Hollfelder
Nov 5, 2016·Expert Opinion on Drug Discovery·Rumin Zhang, Kenny Wong
Oct 7, 2005·Journal of Enzyme Inhibition and Medicinal Chemistry·C Garrido-Del SoloR Varón
Jan 10, 2014·Chembiochem : a European Journal of Chemical Biology·Darja LavoginaAsko Uri
Jul 9, 2008·Journal of Enzyme Inhibition and Medicinal Chemistry·Y B RyuK H Park
Aug 5, 2010·Dalton Transactions : an International Journal of Inorganic Chemistry·Vincenzo AbbatePeter G Taylor
Sep 19, 2006·The Journal of Biological Chemistry·Mark S Sharpley, Judy Hirst
Dec 2, 2017·Nature Reviews. Drug Discovery·Geoffrey A HoldgateRachel L Grimley
Apr 30, 2008·The Journal of Biological Chemistry·Carl Frieden
Oct 20, 2020·International Journal of Biological Macromolecules·Abdul Bari ShahKi Hun Park
Jul 28, 2020·Neuropharmacology·Sofya V Lushchekina, Patrick Masson
Apr 15, 2014·Molecular Pharmaceutics·Mallory A van DongenMark M Banaszak Holl
Jan 5, 2005·Biochemistry·Glenn S Van AllerZhihong Lai
Jul 14, 2005·Journal of the American Chemical Society·Luiz P S de CarvalhoJohn S Blanchard

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