Probing the elusive catalytic activity of vertebrate class IIa histone deacetylases

Bioorg Med Chem Lett. 2008 Mar 15;18(6):1814-9. doi: 10.1016/j.bmcl.2008.02.025. Epub 2008 Feb 14.

Abstract

It has been widely debated whether class IIa HDACs have catalytic deacetylase activity, and whether this plays any part in controlling gene expression. Herein, it has been demonstrated that class IIa HDACs isolated from mammalian cells are contaminated with other deacetylases, but can be prepared cleanly in Escherichia coli. These bacteria preparations have weak but measurable deacetylase activity. The low efficiency can be restored either by: mutation of an active site histidine to tyrosine, or by the use of a non-acetylated lysine substrate, allowing the development of assays to identify class IIa HDAC inhibitors.

Publication types

  • Comparative Study

MeSH terms

  • Acetylation
  • Benzamides / pharmacology
  • Catalysis
  • Cells, Cultured
  • Escherichia coli / enzymology
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases / classification
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Humans
  • Hydroxamic Acids / pharmacology
  • Kidney / enzymology
  • Molecular Structure
  • Mutation
  • Peptides, Cyclic / pharmacology
  • Pyridines / pharmacology
  • Pyrimidines / pharmacology
  • Sulfonamides

Substances

  • Benzamides
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • LAQ824
  • Peptides, Cyclic
  • Pyridines
  • Pyrimidines
  • Sulfonamides
  • apicidin
  • entinostat
  • mocetinostat
  • Histone Deacetylases
  • belinostat