|
|
| (6 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==JMJD2A COMPLEXED WITH NI(II), NOG AND HISTONE H3K27me3 PEPTIDE (25-29) ARK(me3)SA== | | ==JMJD2A COMPLEXED WITH NI(II), NOG AND HISTONE H3K27me3 PEPTIDE (25-29) ARK(me3)SA== |
| - | <StructureSection load='4v2v' size='340' side='right' caption='[[4v2v]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='4v2v' size='340' side='right'caption='[[4v2v]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4v2v]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4V2V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4V2V FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4v2v]] is a 4 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=4V2V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4V2V FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=M3L:N-TRIMETHYLLYSINE'>M3L</scene></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=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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4v2w|4v2w]]</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=4v2v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4v2v OCA], [https://pdbe.org/4v2v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4v2v RCSB], [https://www.ebi.ac.uk/pdbsum/4v2v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4v2v ProSAT]</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=4v2v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4v2v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4v2v RCSB], [http://www.ebi.ac.uk/pdbsum/4v2v PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/KDM4A_HUMAN KDM4A_HUMAN] Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. Participates in transcriptional repression of ASCL2 and E2F-responsive promoters via the recruitment of histone deacetylases and NCOR1, respectively.<ref>PMID:16024779</ref> <ref>PMID:16603238</ref> <ref>PMID:21694756</ref> Isoform 2: Crucial for muscle differentiation, promotes transcriptional activation of the Myog gene by directing the removal of repressive chromatin marks at its promoter. Lacks the N-terminal demethylase domain.<ref>PMID:16024779</ref> <ref>PMID:16603238</ref> <ref>PMID:21694756</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The JmjC-domain-containing 2-oxoglutarate-dependent oxygenases catalyze protein hydroxylation and N()-methyllysine demethylation via hydroxylation. A subgroup of this family, the JmjC lysine demethylases (JmjC KDMs) are involved in histone modifications at multiple sites. There are conflicting reports as to the substrate selectivity of some JmjC oxygenases with respect to KDM activities. In this study, a panel of modified histone H3 peptides was tested for demethylation against 15 human JmjC-domain-containing proteins. The results largely confirmed known N()-methyllysine substrates. However, the purified KDM4 catalytic domains showed greater substrate promiscuity than previously reported (i.e., KDM4A was observed to catalyze demethylation at H3K27 as well as H3K9/K36). Crystallographic analyses revealed that the N()-methyllysine of an H3K27me3 peptide binds similarly to N()-methyllysines of H3K9me3/H3K36me3 with KDM4A. A subgroup of JmjC proteins known to catalyze hydroxylation did not display demethylation activity. Overall, the results reveal that the catalytic domains of the KDM4 enzymes may be less selective than previously identified. They also draw a distinction between the N()-methyllysine demethylation and hydroxylation activities within the JmjC subfamily. These results will be of use to those working on functional studies of the JmjC enzymes. |
| | + | |
| | + | Studies on the catalytic domains of multiple JmjC oxygenases using peptide substrates.,Williams ST, Walport LJ, Hopkinson RJ, Madden SK, Chowdhury R, Schofield CJ, Kawamura A Epigenetics. 2014 Dec 2;9(12):1596-603. doi: 10.4161/15592294.2014.983381. PMID:25625844<ref>PMID:25625844</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 4v2v" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Jumonji domain-containing protein 3D structures|Jumonji domain-containing protein 3D structures]] |
| | + | == References == |
| | + | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Chowdhury, R.]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Madden, S K.]] | + | [[Category: Large Structures]] |
| - | [[Category: Schofield, C J.]] | + | [[Category: Chowdhury R]] |
| - | [[Category: 2-oxoglutarate]] | + | [[Category: Madden SK]] |
| - | [[Category: Chromatin regulator]] | + | [[Category: Schofield CJ]] |
| - | [[Category: Dioxygenase]]
| + | |
| - | [[Category: Double-stranded beta helix]]
| + | |
| - | [[Category: Dsbh]]
| + | |
| - | [[Category: Epigenetic and transcription regulation]]
| + | |
| - | [[Category: Facial triad]]
| + | |
| - | [[Category: Hydroxylation]]
| + | |
| - | [[Category: Iron]]
| + | |
| - | [[Category: Jmjc domain]]
| + | |
| - | [[Category: Metal binding protein]]
| + | |
| - | [[Category: Non-heme]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Oxygenase]]
| + | |
| Structural highlights
4v2v is a 4 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 2Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
KDM4A_HUMAN Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. Participates in transcriptional repression of ASCL2 and E2F-responsive promoters via the recruitment of histone deacetylases and NCOR1, respectively.[1] [2] [3] Isoform 2: Crucial for muscle differentiation, promotes transcriptional activation of the Myog gene by directing the removal of repressive chromatin marks at its promoter. Lacks the N-terminal demethylase domain.[4] [5] [6]
Publication Abstract from PubMed
The JmjC-domain-containing 2-oxoglutarate-dependent oxygenases catalyze protein hydroxylation and N()-methyllysine demethylation via hydroxylation. A subgroup of this family, the JmjC lysine demethylases (JmjC KDMs) are involved in histone modifications at multiple sites. There are conflicting reports as to the substrate selectivity of some JmjC oxygenases with respect to KDM activities. In this study, a panel of modified histone H3 peptides was tested for demethylation against 15 human JmjC-domain-containing proteins. The results largely confirmed known N()-methyllysine substrates. However, the purified KDM4 catalytic domains showed greater substrate promiscuity than previously reported (i.e., KDM4A was observed to catalyze demethylation at H3K27 as well as H3K9/K36). Crystallographic analyses revealed that the N()-methyllysine of an H3K27me3 peptide binds similarly to N()-methyllysines of H3K9me3/H3K36me3 with KDM4A. A subgroup of JmjC proteins known to catalyze hydroxylation did not display demethylation activity. Overall, the results reveal that the catalytic domains of the KDM4 enzymes may be less selective than previously identified. They also draw a distinction between the N()-methyllysine demethylation and hydroxylation activities within the JmjC subfamily. These results will be of use to those working on functional studies of the JmjC enzymes.
Studies on the catalytic domains of multiple JmjC oxygenases using peptide substrates.,Williams ST, Walport LJ, Hopkinson RJ, Madden SK, Chowdhury R, Schofield CJ, Kawamura A Epigenetics. 2014 Dec 2;9(12):1596-603. doi: 10.4161/15592294.2014.983381. PMID:25625844[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhang D, Yoon HG, Wong J. JMJD2A is a novel N-CoR-interacting protein and is involved in repression of the human transcription factor achaete scute-like homologue 2 (ASCL2/Hash2). Mol Cell Biol. 2005 Aug;25(15):6404-14. PMID:16024779 doi:http://dx.doi.org/25/15/6404
- ↑ Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z, Spooner E, Li E, Zhang G, Colaiacovo M, Shi Y. Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell. 2006 May 5;125(3):467-81. Epub 2006 Apr 6. PMID:16603238 doi:10.1016/j.cell.2006.03.028
- ↑ Verrier L, Escaffit F, Chailleux C, Trouche D, Vandromme M. A new isoform of the histone demethylase JMJD2A/KDM4A is required for skeletal muscle differentiation. PLoS Genet. 2011 Jun;7(6):e1001390. doi: 10.1371/journal.pgen.1001390. Epub 2011 , Jun 2. PMID:21694756 doi:http://dx.doi.org/10.1371/journal.pgen.1001390
- ↑ Zhang D, Yoon HG, Wong J. JMJD2A is a novel N-CoR-interacting protein and is involved in repression of the human transcription factor achaete scute-like homologue 2 (ASCL2/Hash2). Mol Cell Biol. 2005 Aug;25(15):6404-14. PMID:16024779 doi:http://dx.doi.org/25/15/6404
- ↑ Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z, Spooner E, Li E, Zhang G, Colaiacovo M, Shi Y. Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell. 2006 May 5;125(3):467-81. Epub 2006 Apr 6. PMID:16603238 doi:10.1016/j.cell.2006.03.028
- ↑ Verrier L, Escaffit F, Chailleux C, Trouche D, Vandromme M. A new isoform of the histone demethylase JMJD2A/KDM4A is required for skeletal muscle differentiation. PLoS Genet. 2011 Jun;7(6):e1001390. doi: 10.1371/journal.pgen.1001390. Epub 2011 , Jun 2. PMID:21694756 doi:http://dx.doi.org/10.1371/journal.pgen.1001390
- ↑ Williams ST, Walport LJ, Hopkinson RJ, Madden SK, Chowdhury R, Schofield CJ, Kawamura A. Studies on the catalytic domains of multiple JmjC oxygenases using peptide substrates. Epigenetics. 2014 Dec 2;9(12):1596-603. doi: 10.4161/15592294.2014.983381. PMID:25625844 doi:http://dx.doi.org/10.4161/15592294.2014.983381
|
