3avr: Difference between revisions
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< | ==Catalytic fragment of UTX/KDM6A bound with histone H3K27me3 peptide, N-oxyalylglycine, and Ni(II)== | ||
<StructureSection load='3avr' size='340' side='right'caption='[[3avr]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3avr]] 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=3AVR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3AVR FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.803Å</td></tr> | |||
- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=M3L:N-TRIMETHYLLYSINE'>M3L</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</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'>[https://proteopedia.org/fgij/fg.htm?mol=3avr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3avr OCA], [https://pdbe.org/3avr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3avr RCSB], [https://www.ebi.ac.uk/pdbsum/3avr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3avr ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/H31_HUMAN H31_HUMAN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Tri- and dimethylations of histone H3K9 (H3K9me3/2) and H3K27 (H3K27me3/2), both situated in the "A-R-Kme-S" sequence motif, mediate transcriptional repression of distinct genomic regions. H3K9me3/2 mainly governs constitutive heterochromatin formation, while H3K27me3/2 represses key developmental genes. The mechanisms by which histone-modifying enzymes selectively regulate the methylation states of H3K9 and H3K27 are poorly understood. Here we report the crystal structures of the catalytic fragment of UTX/KDM6A, an H3K27me3/2-specific demethylase, in the free and H3 peptide-bound forms. The catalytic jumonji domain binds H3 residues 25-33, recognizing H3R26, H3A29, and H3P30 in a sequence-specific manner, in addition to H3K27me3 in the catalytic pocket. A novel zinc-binding domain, conserved within the KDM6 family, binds residues 17-21 of H3. The zinc-binding domain changes its conformation upon H3 binding, and thereby recognizes the H3L20 side chain via a hydrophobic patch on its surface, which is inaccessible in the H3-free form. Mutational analyses showed that H3R17, H3L20, H3R26, H3A29, H3P30, and H3T32 are each important for demethylation. No other methyllysines in the histone tails have the same set of residues at the corresponding positions. Thus, we clarified how UTX discriminates H3K27me3/2 from the other methyllysines with distinct roles, including the near-cognate H3K9me3/2, in histones. | |||
Structural basis for histone H3 Lys 27 demethylation by UTX/KDM6A.,Sengoku T, Yokoyama S Genes Dev. 2011 Nov 1;25(21):2266-77. Epub 2011 Oct 14. PMID:22002947<ref>PMID:22002947</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3avr" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
[[ | *[[Lysine-specific histone demethylase 3D structures|Lysine-specific histone demethylase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Sengoku T]] | ||
[[Category: | [[Category: Yokoyama S]] | ||
Latest revision as of 18:58, 4 October 2023
Catalytic fragment of UTX/KDM6A bound with histone H3K27me3 peptide, N-oxyalylglycine, and Ni(II)Catalytic fragment of UTX/KDM6A bound with histone H3K27me3 peptide, N-oxyalylglycine, and Ni(II)
Structural highlights
FunctionPublication Abstract from PubMedTri- and dimethylations of histone H3K9 (H3K9me3/2) and H3K27 (H3K27me3/2), both situated in the "A-R-Kme-S" sequence motif, mediate transcriptional repression of distinct genomic regions. H3K9me3/2 mainly governs constitutive heterochromatin formation, while H3K27me3/2 represses key developmental genes. The mechanisms by which histone-modifying enzymes selectively regulate the methylation states of H3K9 and H3K27 are poorly understood. Here we report the crystal structures of the catalytic fragment of UTX/KDM6A, an H3K27me3/2-specific demethylase, in the free and H3 peptide-bound forms. The catalytic jumonji domain binds H3 residues 25-33, recognizing H3R26, H3A29, and H3P30 in a sequence-specific manner, in addition to H3K27me3 in the catalytic pocket. A novel zinc-binding domain, conserved within the KDM6 family, binds residues 17-21 of H3. The zinc-binding domain changes its conformation upon H3 binding, and thereby recognizes the H3L20 side chain via a hydrophobic patch on its surface, which is inaccessible in the H3-free form. Mutational analyses showed that H3R17, H3L20, H3R26, H3A29, H3P30, and H3T32 are each important for demethylation. No other methyllysines in the histone tails have the same set of residues at the corresponding positions. Thus, we clarified how UTX discriminates H3K27me3/2 from the other methyllysines with distinct roles, including the near-cognate H3K9me3/2, in histones. Structural basis for histone H3 Lys 27 demethylation by UTX/KDM6A.,Sengoku T, Yokoyama S Genes Dev. 2011 Nov 1;25(21):2266-77. Epub 2011 Oct 14. PMID:22002947[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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