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| | <StructureSection load='4qxc' size='340' side='right'caption='[[4qxc]], [[Resolution|resolution]] 1.75Å' scene=''> | | <StructureSection load='4qxc' size='340' side='right'caption='[[4qxc]], [[Resolution|resolution]] 1.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4qxc]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QXC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QXC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4qxc]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QXC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QXC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</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=4qxc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qxc OCA], [https://pdbe.org/4qxc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qxc RCSB], [https://www.ebi.ac.uk/pdbsum/4qxc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qxc ProSAT]</span></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4tn7|4tn7]], [[2yu1|2yu1]], [[2yu2|2yu2]], [[4qx7|4qx7]], [[4qx8|4qx8]], [[4qxb|4qxb]], [[4qxh|4qxh]], [[4qwn|4qwn]]</td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Kdm2a, Fbxl11, Jhdm1a, Kiaa1004 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/[Histone_H3]-lysine-36_demethylase [Histone H3]-lysine-36 demethylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.11.27 1.14.11.27] </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=4qxc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qxc OCA], [http://pdbe.org/4qxc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qxc RCSB], [http://www.ebi.ac.uk/pdbsum/4qxc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qxc ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/KDM2A_MOUSE KDM2A_MOUSE] Histone demethylase that specifically demethylates 'Lys-36' of histone H3, thereby playing a central role in histone code. Preferentially demethylates dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36'. May also recognize and bind to some phosphorylated proteins and promote their ubiquitination and degradation. Required to maintain the heterochromatic state. Associates with centromeres and represses transcription of small non-coding RNAs that are encoded by the clusters of satellite repeats at the centromere. Required to sustain centromeric integrity and genomic stability, particularly during mitosis (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Jumonji domain-containing protein|Jumonji domain-containing protein]] | + | *[[Jumonji domain-containing protein 3D structures|Jumonji domain-containing protein 3D structures]] |
| - | *[[Lysine-specific histone demethylase|Lysine-specific histone demethylase]] | + | *[[Lysine-specific histone demethylase 3D structures|Lysine-specific histone demethylase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Cheng, Z J]] | + | [[Category: Cheng ZJ]] |
| - | [[Category: Patel, D J]] | + | [[Category: Patel DJ]] |
| - | [[Category: Histone demethylase]]
| + | |
| - | [[Category: Jmjc domain]]
| + | |
| - | [[Category: Oxidoreductase-structural protein complex]]
| + | |
| Structural highlights
Function
KDM2A_MOUSE Histone demethylase that specifically demethylates 'Lys-36' of histone H3, thereby playing a central role in histone code. Preferentially demethylates dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36'. May also recognize and bind to some phosphorylated proteins and promote their ubiquitination and degradation. Required to maintain the heterochromatic state. Associates with centromeres and represses transcription of small non-coding RNAs that are encoded by the clusters of satellite repeats at the centromere. Required to sustain centromeric integrity and genomic stability, particularly during mitosis (By similarity).
Publication Abstract from PubMed
The dynamic reversible methylation of lysine residues on histone proteins is central to chromatin biology. Key components are demethylase enzymes, which remove methyl moieties from lysine residues. KDM2A, a member of the Jumonji C domain-containing histone lysine demethylase family, specifically targets lower methylation states of H3K36. Here, structural studies reveal that H3K36 specificity for KDM2A is mediated by the U-shaped threading of the H3K36 peptide through a catalytic groove within KDM2A. The side chain of methylated K36 inserts into the catalytic pocket occupied by Ni(2+) and cofactor, where it is positioned and oriented for demethylation. Key residues contributing to K36me specificity on histone H3 are G33 and G34 (positioned within a narrow channel), P38 (a turn residue), and Y41 (inserts into its own pocket). Given that KDM2A was found to also bind the H3K36me3 peptide, we postulate that steric constraints could prevent alpha-ketoglutarate from undergoing an "off-line"-to-"in-line" transition necessary for the demethylation reaction. Furthermore, structure-guided substitutions of residues in the KDM2A catalytic pocket abrogate KDM2A-mediated functions important for suppression of cancer cell phenotypes. Together, our results deduce insights into the molecular basis underlying KDM2A regulation of the biologically important methylated H3K36 mark.
A molecular threading mechanism underlies Jumonji lysine demethylase KDM2A regulation of methylated H3K36.,Cheng Z, Cheung P, Kuo AJ, Yukl ET, Wilmot CM, Gozani O, Patel DJ Genes Dev. 2014 Aug 15;28(16):1758-71. doi: 10.1101/gad.246561.114. PMID:25128496[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Cheng Z, Cheung P, Kuo AJ, Yukl ET, Wilmot CM, Gozani O, Patel DJ. A molecular threading mechanism underlies Jumonji lysine demethylase KDM2A regulation of methylated H3K36. Genes Dev. 2014 Aug 15;28(16):1758-71. doi: 10.1101/gad.246561.114. PMID:25128496 doi:http://dx.doi.org/10.1101/gad.246561.114
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