Determination of the binding mechanism of histone deacetylase inhibitors

This article contains a comprehensive collection of methods and protocols that enables the elucidation of the binding mechanism of inhibitors to histone deacetylases. All available equilibrium and kinetic data can be beneficially combined in a data analysis procedure called Integrated Global Fit analysis eventually yielding the most likely binding mechanism. AbstractThis article places its focus on methods and tools enabling the elucidation of the mechanism by which ligands, small molecule inhibitors or substrates, interact with zinc containing bacterial or human members of the histone deacetylase family (HDACs). These methods include biochemical and biophysical approaches and can be subdivided into equilibrium and kinetic methods. More information about the exact mode of action can be obtained by combining these methods with specific mutant variants of the enzymes and/or series of structural similar ligands. All available equilibrium and kinetic data including additional information from 3D ‐structures of HDAC‐ligand complexes can be beneficially combined in a data analysis procedure called Integrated Global Fit analysis eventually providing the most likely binding mechanism.This article is protected by copyright. All rights reserved.

Source: Chemical Biology and Drug Design - November 27, 2018 Category: Biology Authors: Franz ‐Josef Meyer‐Almes Tags: Special Issue Article Source Type: research