Plant growth regulator daminozide is a selective inhibitor of human KDM2/7 histone demethylases.

ABSTRACT: The JmjC oxygenases catalyze the N-demethylation of N(ε)-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 (N-(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.

SUBMITTER: Rose NR 

PROVIDER: S-EPMC4673902 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature