Determination of the binding mechanism of histone deacetylase inhibitors.

This 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.
(© 2018 John Wiley & Sons A/S.)