4uf0
From Proteopedia
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==Crystal structure of JmjC domain of human histone demethylase UTY in complex with epitherapuetic compound 2-(((2-((2-(dimethylamino)ethyl) (ethyl)amino)-2-oxoethyl)amino)methyl)isonicotinic acid.== | ==Crystal structure of JmjC domain of human histone demethylase UTY in complex with epitherapuetic compound 2-(((2-((2-(dimethylamino)ethyl) (ethyl)amino)-2-oxoethyl)amino)methyl)isonicotinic acid.== | ||
<StructureSection load='4uf0' size='340' side='right' caption='[[4uf0]], [[Resolution|resolution]] 1.78Å' scene=''> | <StructureSection load='4uf0' size='340' side='right' caption='[[4uf0]], [[Resolution|resolution]] 1.78Å' scene=''> | ||
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<table><tr><td colspan='2'>[[4uf0]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UF0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UF0 FirstGlance]. <br> | <table><tr><td colspan='2'>[[4uf0]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UF0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UF0 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=MMK:2-{[(2-{[(E)-2-(DIMETHYLAMINO)ETHENYL](ETHYL)AMINO}-2-OXOETHYL)AMINO]METHYL}PYRIDINE-4-CARBOXYLIC+ACID'>MMK</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=MMK:2-{[(2-{[(E)-2-(DIMETHYLAMINO)ETHENYL](ETHYL)AMINO}-2-OXOETHYL)AMINO]METHYL}PYRIDINE-4-CARBOXYLIC+ACID'>MMK</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=4uf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uf0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4uf0 RCSB], [http://www.ebi.ac.uk/pdbsum/4uf0 PDBsum]</span></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=4uf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uf0 OCA], [http://pdbe.org/4uf0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4uf0 RCSB], [http://www.ebi.ac.uk/pdbsum/4uf0 PDBsum]</span></td></tr> |
</table> | </table> | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/UTY_HUMAN UTY_HUMAN]] Histone demethylase (By similarity). | [[http://www.uniprot.org/uniprot/UTY_HUMAN UTY_HUMAN]] Histone demethylase (By similarity). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Members of the KDM5 (also known as JARID1) family are 2-oxoglutarate- and Fe2+-dependent oxygenases that act as histone H3K4 demethylases, thereby regulating cell proliferation and stem cell self-renewal and differentiation. Here we report crystal structures of the catalytic core of the human KDM5B enzyme in complex with three inhibitor chemotypes. These scaffolds exploit several aspects of the KDM5 active site, and their selectivity profiles reflect their hybrid features with respect to the KDM4 and KDM6 families. Whereas GSK-J1, a previously identified KDM6 inhibitor, showed about sevenfold less inhibitory activity toward KDM5B than toward KDM6 proteins, KDM5-C49 displayed 25-100-fold selectivity between KDM5B and KDM6B. The cell-permeable derivative KDM5-C70 had an antiproliferative effect in myeloma cells, leading to genome-wide elevation of H3K4me3 levels. The selective inhibitor GSK467 exploited unique binding modes, but it lacked cellular potency in the myeloma system. Taken together, these structural leads deliver multiple starting points for further rational and selective inhibitor design. | ||
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| + | Structural analysis of human KDM5B guides histone demethylase inhibitor development.,Johansson C, Velupillai S, Tumber A, Szykowska A, Hookway ES, Nowak RP, Strain-Damerell C, Gileadi C, Philpott M, Burgess-Brown N, Wu N, Kopec J, Nuzzi A, Steuber H, Egner U, Badock V, Munro S, LaThangue NB, Westaway S, Brown J, Athanasou N, Prinjha R, Brennan PE, Oppermann U Nat Chem Biol. 2016 May 23. doi: 10.1038/nchembio.2087. PMID:27214403<ref>PMID:27214403</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4uf0" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 08:15, 1 June 2016
Crystal structure of JmjC domain of human histone demethylase UTY in complex with epitherapuetic compound 2-(((2-((2-(dimethylamino)ethyl) (ethyl)amino)-2-oxoethyl)amino)methyl)isonicotinic acid.
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