View source for 2ybk


==JMJD2A COMPLEXED WITH R-2-HYDROXYGLUTARATE==
<StructureSection load='2ybk' size='340' side='right' caption='[[2ybk]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ybk]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YBK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YBK FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2HG:(2R)-2-HYDROXYPENTANEDIOIC+ACID'>2HG</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wwj|2wwj]], [[2gfa|2gfa]], [[2vd7|2vd7]], [[2ybs|2ybs]], [[2ybp|2ybp]], [[2gp3|2gp3]], [[2gf7|2gf7]], [[2gp5|2gp5]]</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ybk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ybk OCA], [http://pdbe.org/2ybk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ybk RCSB], [http://www.ebi.ac.uk/pdbsum/2ybk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ybk ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/KDM4A_HUMAN 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.<ref>PMID:16024779</ref> <ref>PMID:16603238</ref> <ref>PMID:21694756</ref>   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.<ref>PMID:16024779</ref> <ref>PMID:16603238</ref> <ref>PMID:21694756</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mutations in isocitrate dehydrogenases (IDHs) have a gain-of-function effect leading to R(-)-2-hydroxyglutarate (R-2HG) accumulation. By using biochemical, structural and cellular assays, we show that either or both R- and S-2HG inhibit 2-oxoglutarate (2OG)-dependent oxygenases with varying potencies. Half-maximal inhibitory concentration (IC(50)) values for the R-form of 2HG varied from approximately 25 muM for the histone N(varepsilon)-lysine demethylase JMJD2A to more than 5 mM for the hypoxia-inducible factor (HIF) prolyl hydroxylase. The results indicate that candidate oncogenic pathways in IDH-associated malignancy should include those that are regulated by other 2OG oxygenases than HIF hydroxylases, in particular those involving the regulation of histone methylation.

The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases.,Chowdhury R, Yeoh KK, Tian YM, Hillringhaus L, Bagg EA, Rose NR, Leung IK, Li XS, Woon EC, Yang M, McDonough MA, King ON, Clifton IJ, Klose RJ, Claridge TD, Ratcliffe PJ, Schofield CJ, Kawamura A EMBO Rep. 2011 May 1;12(5):463-9. Epub 2011 Apr 1. PMID:21460794<ref>PMID:21460794</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2ybk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Chowdhury, R]]
[[Category: McDonough, M A]]
[[Category: Schofield, C J]]
[[Category: 2-oxoglutarate]]
[[Category: Chromatin regulator]]
[[Category: Dioxygenase]]
[[Category: Double-stranded beta helix]]
[[Category: Dsbh]]
[[Category: Epigenetic and transcription regulation]]
[[Category: Facial triad]]
[[Category: Hydroxylation]]
[[Category: Iron]]
[[Category: Metal binding protein]]
[[Category: Non-heme]]
[[Category: Oxidoreductase]]
[[Category: Oxygenase]]