5fwj

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==Crystal structure of human JARID1C in complex with KDM5-C49==
==Crystal structure of human JARID1C in complex with KDM5-C49==
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<StructureSection load='5fwj' size='340' side='right' caption='[[5fwj]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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<StructureSection load='5fwj' size='340' side='right'caption='[[5fwj]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5fwj]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FWJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FWJ FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5fwj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FWJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FWJ FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
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<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=5fwj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fwj OCA], [http://pdbe.org/5fwj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fwj RCSB], [http://www.ebi.ac.uk/pdbsum/5fwj PDBsum]</span></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5fwj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fwj OCA], [https://pdbe.org/5fwj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fwj RCSB], [https://www.ebi.ac.uk/pdbsum/5fwj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fwj ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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[[http://www.uniprot.org/uniprot/KDM5C_HUMAN KDM5C_HUMAN]] Syndromic X-linked intellectual disability due to JARID1C mutation. The disease is caused by mutations affecting the gene represented in this entry.
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[https://www.uniprot.org/uniprot/KDM5C_HUMAN KDM5C_HUMAN] Syndromic X-linked intellectual disability due to JARID1C mutation. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/KDM5C_HUMAN KDM5C_HUMAN]] Histone demethylase that specifically demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. Participates in transcriptional repression of neuronal genes by recruiting histone deacetylases and REST at neuron-restrictive silencer elements. Represses the CLOCK-ARNTL/BMAL1 heterodimer-mediated transcriptional activation of the core clock component PER2 (By similarity).[UniProtKB:P41230]<ref>PMID:17320160</ref> <ref>PMID:17320161</ref> <ref>PMID:17468742</ref>
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[https://www.uniprot.org/uniprot/KDM5C_HUMAN KDM5C_HUMAN] Histone demethylase that specifically demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. Participates in transcriptional repression of neuronal genes by recruiting histone deacetylases and REST at neuron-restrictive silencer elements. Represses the CLOCK-ARNTL/BMAL1 heterodimer-mediated transcriptional activation of the core clock component PER2 (By similarity).[UniProtKB:P41230]<ref>PMID:17320160</ref> <ref>PMID:17320161</ref> <ref>PMID:17468742</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 5fwj" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Jumonji domain-containing protein 3D structures|Jumonji domain-containing protein 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Arrowsmith, C H]]
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[[Category: Homo sapiens]]
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[[Category: Bountra, C]]
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[[Category: Large Structures]]
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[[Category: Burgess-Brown, N A]]
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[[Category: Arrowsmith CH]]
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[[Category: Dong, W]]
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[[Category: Bountra C]]
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[[Category: Edwards, A]]
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[[Category: Burgess-Brown NA]]
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[[Category: Gileadi, C]]
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[[Category: Dong W]]
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[[Category: Huber, K]]
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[[Category: Edwards A]]
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[[Category: Johansson, C]]
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[[Category: Gileadi C]]
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[[Category: Kopec, J]]
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[[Category: Huber K]]
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[[Category: Kupinska, K]]
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[[Category: Johansson C]]
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[[Category: Nowak, R]]
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[[Category: Kopec J]]
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[[Category: Oppermann, U]]
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[[Category: Kupinska K]]
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[[Category: Shrestha, L]]
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[[Category: Nowak R]]
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[[Category: Srikannathasan, V]]
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[[Category: Oppermann U]]
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[[Category: Strain-Damerell, C]]
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[[Category: Shrestha L]]
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[[Category: Szykowska, A]]
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[[Category: Srikannathasan V]]
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[[Category: VonDELFT, F]]
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[[Category: Strain-Damerell C]]
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[[Category: Lysine-specific]]
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[[Category: Szykowska A]]
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[[Category: Lysine-specific demethylase 5c]]
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[[Category: Von Delft F]]
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[[Category: Oxidoreductase]]
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Current revision

Crystal structure of human JARID1C in complex with KDM5-C49

PDB ID 5fwj

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