| Literature DB >> 22724510 |
Nathan R Rose1, Esther C Y Woon, Anthony Tumber, Louise J Walport, Rasheduzzaman Chowdhury, Xuan Shirley Li, Oliver N F King, Clarisse Lejeune, Stanley S Ng, Tobias Krojer, Mun Chiang Chan, Anna M Rydzik, Richard J Hopkinson, Ka Hing Che, Michelle Daniel, Claire Strain-Damerell, Carina Gileadi, Grazyna Kochan, Ivanhoe K H Leung, James Dunford, Kar Kheng Yeoh, Peter J Ratcliffe, Nicola Burgess-Brown, Frank von Delft, Susanne Muller, Brian Marsden, Paul E Brennan, Michael A McDonough, Udo Oppermann, Robert J Klose, Christopher J Schofield, Akane Kawamura.
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.Entities:
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Year: 2012 PMID： 22724510 PMCID： PMC4673902 DOI： 10.1021/jm300677j
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446