4ai9

JMJD2A COMPLEXED WITH DAMINOZIDE

spinqualitylabelsall models 4ai9, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ai9 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, DZA, GOL, NI, ZN Related: 2gf7, 2gfa, 2gp3, 2gp5, 2vd7, 2wwj, 2ybk, 2ybp, 2ybs Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [KDM4A_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. 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. Publication Abstract from PubMed The JmjC oxygenases catalyze the N-demethylation of N(epsilon)-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. Plant growth regulator daminozide is a selective inhibitor of human KDM2/7 histone demethylases.,Rose NR, Woon EC, Tumber A, Walport LJ, Chowdhury R, Li XS, King ON, Lejeune C, Ng SS, Krojer T, Chan MC, Rydzik AM, Hopkinson RJ, Che KH, Daniel M, Strain-Damerell C, Gileadi C, Kochan G, Leung IK, Dunford J, Yeoh KK, Ratcliffe PJ, Burgess-Brown N, von Delft F, Muller S, Marsden B, Brennan PE, McDonough MA, Oppermann U, Klose RJ, Schofield CJ, Kawamura A J Med Chem. 2012 Jul 26;55(14):6639-43. Epub 2012 Jul 11. PMID:22724510 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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