Plant Growth Regulator
Daminozide Is a Selective Inhibitor
of Human KDM2/7 Histone Demethylases
- Publication date
- Publisher
Abstract
The JmjC oxygenases catalyze the <i>N</i>-demethylation
of <i>N</i><sup>ε</sup>-methyl lysine residues in
histones and are current therapeutic targets. A set of human 2-oxoglutarate
analogues were screened using
a unified assay platform for JmjC demethylases and related oxygenases.
Results led to the finding that daminozide (<i>N-</i>(dimethylamino)succinamic
acid, 160 Da), a plant growth regulator, selectively inhibits the
KDM2/7 JmjC subfamily. Kinetic and crystallographic studies reveal
that daminozide chelates the active site metal via its hydrazide carbonyl
and dimethylamino groups
