Allosteric binding cooperativity in a kinetic context

Cita com:
hdl:2117/378432
Document typeArticle
Defense date2023-02
Rights accessOpen Access
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Attribution 4.0 International
Abstract
Allosteric modulators are of prime interest in drug discovery. These drugs regulate the binding and function of endogenous ligands, with some advantages over orthosteric ligands. A typical pharmacological parameter in allosteric modulation is binding cooperativity. This property can yield unexpected but illuminating results when decomposed into its kinetic parameters. Using two reference models (the allosteric ternary complex receptor model and a heterodimer receptor model), a relationship has been derived for the cooperativity rate constant parameters. This relationship allows many combinations of the cooperativity kinetic parameters for a single binding cooperativity value obtained under equilibrium conditions. This assessment may help understand striking experimental results involving allosteric modulation and suggest further investigations in the field
CitationDíaz, Ó. [et al.]. Allosteric binding cooperativity in a kinetic context. "Drug discovery today", Febrer 2023, vol. 28, núm. 2, 103441.
ISSN1359-6446
Other identifiershttps://www.sciencedirect.com/science/article/pii/S1359644622004342
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