4ura
From Proteopedia
Crystal structure of human JMJD2A in complex with compound 14a
Structural highlights
FunctionKDM4A_HUMAN Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. Participates in transcriptional repression of ASCL2 and E2F-responsive promoters via the recruitment of histone deacetylases and NCOR1, respectively.[1] [2] [3] Isoform 2: Crucial for muscle differentiation, promotes transcriptional activation of the Myog gene by directing the removal of repressive chromatin marks at its promoter. Lacks the N-terminal demethylase domain.[4] [5] [6] Publication Abstract from PubMedA potent inhibitor of the JmjC histone lysine demethylase KDM2A (compound 35, pIC50 7.2) with excellent selectivity over representatives from other KDM subfamilies has been developed; the discovery that a triazolopyridine compound binds to the active site of JmjC KDMs was followed by optimisation of the triazole substituent for KDM2A inhibition and selectivity. Optimisation of a triazolopyridine based histone demethylase inhibitor yields a potent and selective KDM2A (FBXL11) inhibitor.,England KS, Tumber A, Krojer T, Scozzafava G, Ng SS, Daniel M, Szykowska A, Che K, von Delft F, Burgess-Brown NA, Kawamura A, Schofield CJ, Brennan PE Medchemcomm. 2014 Dec 1;5(12):1879-1886. PMID:26682034[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Large Structures | Arrowsmith CH | Bountra C | Brennan PE | Burgess-Brown N | Crawley L | Edwards A | England KS | Krojer T | Oppermann U | Riesebos E | Szykowska A | Vollmar M | Williams E | Von Delft F
