title: Probing the elusive catalytic activity of vertebrate class IIa histone deacetylases.
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.
authors.affiliation: IRBM/Merck Research Laboratories, Via Pontina km 30,600, 00040 Pomezia, Italy. philip_jones@merck.com
authors.forename: Philip
authors.initials: P
authors.lastname: Jones
authors.forename: Sergio
authors.initials: S
authors.lastname: Altamura
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Francesco
authors.forename: Paola
authors.initials: P
authors.lastname: Gallinari
authors.forename: Armin
authors.initials: A
authors.lastname: Lahm
authors.forename: Petra
authors.initials: P
authors.lastname: Neddermann
authors.forename: Michael
authors.initials: M
authors.lastname: Rowley
authors.forename: Sergio
authors.initials: S
authors.lastname: Serafini
authors.forename: Christian
authors.initials: C
authors.lastname: Steinkühler
mesh_terms: D000107:Acetylation; D001549:Benzamides / Q000494:pharmacology; D002384:Catalysis; D002478:Cells, Cultured; D004926:Escherichia coli / Q000201:enzymology; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology; D015394:Molecular Structure; D009154:Mutation; D010456:Peptides, Cyclic / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D013449:Sulfonamides
chemical_list: D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C477361:LAQ824; D010456:Peptides, Cyclic; D011725:Pyridines; D011743:Pyrimidines; D013449:Sulfonamides; C102351:apicidin; C118739:entinostat; C523184:mocetinostat; D006655:Histone Deacetylases; C487081:belinostat