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Equilibrium analysis of allosteric interactions shows zero-order effects.

Vivek K Mutalik·Aditya P Singh·Jeremy S Edwards·K V Venkatesh
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Abstract

The binding of effector to an allosteric protein exhibits a non-Michaelis-Menten behavior, resulting in either ultrasensitive or subsensitive response. In the present work, a modular approach has been developed to determine the response curve for allosteric systems at higher concentration of allosteric enzyme than that of effector (zero-order sensitivity, as observed in enzyme cascades) by equilibrium analysis. The analysis shows that, in an allosteric system, the zero-order effect can make the response ultrasensitive or subsensitive with respect to the enzyme concentration. The response is dependent on the number of binding sites, cooperativity, and the total effector concentration. The framework was further applied to a well studied allosteric protein, the Escherichia coli aspartate transcarbamoylase. The predictions are found to be consistent with the reported experimental data.

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Allosteric RegulationAllosteric SiteAspartate CarbamoyltransferaseBinding SitesBiophysicsCatalytic DomainDose-Response Relationship, DrugEscherichia coliKineticsLigandsModels, StatisticalModels, TheoreticalProtein BindingJournal Article

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Vivek K Mutalik, Aditya P Singh, Jeremy S Edwards, K V Venkatesh. 2004. Equilibrium analysis of allosteric interactions shows zero-order effects.. https://doi.org/10.1385/cbb%3A41%3A2%3A179

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