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An algebraic model for covalent inhibition kinetics
Preprint

An algebraic model for the kinetics of covalent enzyme inhibition at low substrate concentrations

BioKin Technical Note TN-2015-04

Petr Kuzmic
BioKin Ltd.
Draft - Rev. 1.01 - June 15, 2015
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Abstract
This report describes an integrated rate equation for the time-course of covalent enzyme inhibition under the conditions where the substrate concentration is significantly lower than the corresponding Michaelis constant, such as for example in the Omnia assays of EGFR kinase. The newly described method is applicable to experimental conditions where the enzyme concentration is significantly lower than the dissociation constant of the initially formed reversible enzyme-inhibitor complex (no "tight binding"). A detailed comparison with the traditionally used rate equation for covalent inhibition is presented. The two methods produce approximately identical values of the first-order inactivation rate constant (kinact). However, the inhibition constant (Ki) and therefore also the second-order inactivation rate constant kinact/Ki, is underestimated by the traditional method by up to an order of magnitude.
Keywords
enzyme kinetics; mathematics
How to Cite
Kuzmic, P. (2015) Determination of substrate kinetic parameters from progress curve data, Anal. Biochem., In Press [Manuscript No. ABIO-14-632R1]


This Technical Note is the precursor form of an article to be published later in 2015 in the journal Analytical Biochemistry. The current text and illustrations are exactly as originally submitted to the Journal, prior to any editorial changes or other processing performed by the Publisher.
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