PMID: 9445400Mar 7, 1998Paper

Analysis of the combined effect of two linear inhibitors on a single enzyme

The Biochemical Journal
J J Martinez-IrujoE Santiago

Abstract

Different methods for studying the concurrent effects of two linear inhibitors on a single enzyme have been published, including the fractional product of Webb, the Yonetani-Theorell plot or the method of Chou and Talalay. Recently the use of combination plots has also been advocated for this purpose. We have evaluated the applicability of these methods and found that most of them depend on assumptions about the mechanism of action of the inhibitors. If the mechanism of action is not completely understood, or if some assumptions about the mechanism are unfounded, the parameters obtained may be meaningless. Even if these assumptions are correct, the interaction can be advantageously measured using an alternative representation that does not require a knowledge of the inhibition constants and allows experimental data to be retrieved from the plot. In other cases it is the interpretation of the results rather than the validity of the method that is misleading. A common mistake is to take the exclusivity of the effects of two inhibitors as exclusivity of their binding. We show that this assumption is seldom justified. In any case, it is possible to decide whether the combination of two or more inhibitors is more effective than thei...Continue Reading

Citations

Nov 13, 2004·The Biochemical Journal·Jonathan R Gledhill, John E Walker
Aug 22, 2006·Nature Chemical Biology·Jonathan B FitzgeraldPeter K Sorger
Nov 23, 2006·Biotechnology and Bioengineering·Petros Dimitriou-Christidis, Robin L Autenrieth
Jun 10, 2010·Korean journal of anesthesiology·Soo-Il Lee
May 7, 2014·Antimicrobial Agents and Chemotherapy·Amedeo De NicolòAntonio D'Avolio
Jul 11, 2006·The Journal of Biological Chemistry·Carlos CruchagaJuan J Martínez-Irujo
Apr 19, 2018·Journal of Food Science and Technology·Minoli Anuththara Gunasinghe, Sang Moo Kim
May 5, 2007·Journal of Biopharmaceutical Statistics·J J LeeR Lotan
May 29, 2010·The Biochemical Journal·Max W ChangBruce E Torbett
Aug 15, 2014·Journal of Biomolecular Screening·Gustavo F MercaldiArtur T Cordeiro
Sep 9, 2016·Journal of Cellular and Molecular Medicine·Bing HeAiping Lu
Nov 13, 2018·Journal of Medicinal Chemistry·Paul W HeronJurgen Sygusch
Jul 26, 2014·Journal of Medicinal Chemistry·Peter M-U UngHeather A Carlson
Aug 8, 2009·Journal of Theoretical Biology·Patricia Schenker, Antonio Baici

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