Human histone deacetylase 6: profiling of deacylase specificity

Jiri Pavlicek1, Marat Meleshin2, Zsofia Kutil1, Zeljko Simic2, Zora Novakova1, Dalibor Trapl1, Mike Schutkowski2, Cyril Barinka1

1Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prumyslova 595, 25242 Vestec, Czech Republic

2Department of Enzymology, Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Strasse 3, 06120 Halle/Saale (Germany)


In addition to acetylation, several acyl modifications at the lysine side chain were identified in vivo including formylation, propionylation, butyrylation, crotonylation and succinylation. Some sirtuin isoforms were reported to preferentially remove “non-acetyl” functional groups, but there are limited data on the acyl specificity of zinc-dependent histone deacetylases. We systematically mapped the acyl specificity of human histone deacetylase 6 (HDAC6) using a panel of carbamoyl phosphate synthetase1 derived peptides featuring more than 20 acyl modifications. Our data revealed for the first time that in addition to deacetylase, HDAC6 harbors deformylase and depropionylase activities in vitro.  Ensuing structure-function and modeling studied provided further insight into lysine deacylation by HDAC6.