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| | <StructureSection load='5oy3' size='340' side='right'caption='[[5oy3]], [[Resolution|resolution]] 2.14Å' scene=''> | | <StructureSection load='5oy3' size='340' side='right'caption='[[5oy3]], [[Resolution|resolution]] 2.14Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5oy3]] 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=5OY3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OY3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5oy3]] 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=5OY3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OY3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=TBU:TERTIARY-BUTYL+ALCOHOL'>TBU</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.136Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KDM6B, JMJD3, KIAA0346 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=TBU:TERTIARY-BUTYL+ALCOHOL'>TBU</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=5oy3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oy3 OCA], [http://pdbe.org/5oy3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5oy3 RCSB], [http://www.ebi.ac.uk/pdbsum/5oy3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5oy3 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5oy3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oy3 OCA], [https://pdbe.org/5oy3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5oy3 RCSB], [https://www.ebi.ac.uk/pdbsum/5oy3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5oy3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/KDM6B_HUMAN KDM6B_HUMAN]] Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code. Demethylates trimethylated and dimethylated H3 'Lys-27'. Plays a central role in regulation of posterior development, by regulating HOX gene expression. Involved in inflammatory response by participating in macrophage differentiation in case of inflammation by regulating gene expression and macrophage differentiation.<ref>PMID:17825402</ref> <ref>PMID:17851529</ref> | + | [https://www.uniprot.org/uniprot/KDM6B_HUMAN KDM6B_HUMAN] Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code. Demethylates trimethylated and dimethylated H3 'Lys-27'. Plays a central role in regulation of posterior development, by regulating HOX gene expression. Involved in inflammatory response by participating in macrophage differentiation in case of inflammation by regulating gene expression and macrophage differentiation.<ref>PMID:17825402</ref> <ref>PMID:17851529</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5oy3" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5oy3" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Jumonji domain-containing protein 3D structures|Jumonji domain-containing protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gajhede, M]] | + | [[Category: Gajhede M]] |
| - | [[Category: Jones, S E]] | + | [[Category: Jones SE]] |
| - | [[Category: Olsen, L]] | + | [[Category: Olsen L]] |
| - | [[Category: Epigenetic]]
| + | |
| - | [[Category: Histone demethylase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Substrate complex]]
| + | |
| Structural highlights
5oy3 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.136Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
KDM6B_HUMAN Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code. Demethylates trimethylated and dimethylated H3 'Lys-27'. Plays a central role in regulation of posterior development, by regulating HOX gene expression. Involved in inflammatory response by participating in macrophage differentiation in case of inflammation by regulating gene expression and macrophage differentiation.[1] [2]
Publication Abstract from PubMed
KDM subfamily 6 enzymes KDM6A and KDM6B specifically catalyze demethylation of di- and trimethylated lysine on histone 3 lysine 27 (H3K27me3/2) and play an important role in repression of developmental genes. Despite identical amino acid sequence in the immediate surroundings of H3K9me3/2 (ARKS), the enzymes do not catalyze demethylation of this general marker of repression. To address this question for KDM6B, we used computational methods to identify H3(17-33)-derived peptides with improved binding affinity that would allow co-crystallization with the catalytic core of human KDM6B (ccKDM6B). A total of five peptides were identified, and their IC50 values were determined in a matrix-assisted laser desorption ionization time-of-flight-based assay. Despite none of the peptides showing affinity significantly higher than that of the H3(17-33) peptide, it was possible to co-crystallize ccKDM6B with a H3(17-33)A21M peptide. This structure reveals the interactions between the KDM6B zinc binding domain and the H3(17-23) region. Although KDM6A and KDM6B differ in primary sequence, particularly in the H3L20 binding pocket of the zinc binding domains, where two histidines in KDM6A have been replaced by a glutamate and a tyrosine, they bind H3(17-23) in a very similar fashion. This structure shows that KDM6B, in analogy with KDM6A, also uses the zinc binding domain to achieve H3K27me3/me2 specificity. The histidine to glutamine substitution at amino acid position 1564 in the KDM6B zinc binding domain can further explain why KDM6B binds substrates with an affinity higher than that of KDM6A.
Structural Basis of Histone Demethylase KDM6B Histone 3 Lysine 27 Specificity.,Jones SE, Olsen L, Gajhede M Biochemistry. 2018 Feb 6;57(5):585-592. doi: 10.1021/acs.biochem.7b01152. Epub, 2017 Dec 19. PMID:29220567[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ De Santa F, Totaro MG, Prosperini E, Notarbartolo S, Testa G, Natoli G. The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing. Cell. 2007 Sep 21;130(6):1083-94. Epub 2007 Sep 6. PMID:17825402 doi:http://dx.doi.org/S0092-8674(07)01082-3
- ↑ Lan F, Bayliss PE, Rinn JL, Whetstine JR, Wang JK, Chen S, Iwase S, Alpatov R, Issaeva I, Canaani E, Roberts TM, Chang HY, Shi Y. A histone H3 lysine 27 demethylase regulates animal posterior development. Nature. 2007 Oct 11;449(7163):689-94. Epub 2007 Sep 12. PMID:17851529 doi:http://dx.doi.org/10.1038/nature06192
- ↑ Jones SE, Olsen L, Gajhede M. Structural Basis of Histone Demethylase KDM6B Histone 3 Lysine 27 Specificity. Biochemistry. 2018 Feb 6;57(5):585-592. doi: 10.1021/acs.biochem.7b01152. Epub, 2017 Dec 19. PMID:29220567 doi:http://dx.doi.org/10.1021/acs.biochem.7b01152
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