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| | <StructureSection load='3qox' size='340' side='right'caption='[[3qox]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='3qox' size='340' side='right'caption='[[3qox]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3qox]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QOX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QOX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3qox]] is a 1 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=3QOX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QOX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3qow|3qow]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DOT1L, KIAA1814, KMT4 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </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=3qox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qox OCA], [https://pdbe.org/3qox PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qox RCSB], [https://www.ebi.ac.uk/pdbsum/3qox PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qox 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=3qox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qox OCA], [https://pdbe.org/3qox PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qox RCSB], [https://www.ebi.ac.uk/pdbsum/3qox PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qox ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/DOT1L_HUMAN DOT1L_HUMAN]] Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones. Binds to DNA.
| + | [https://www.uniprot.org/uniprot/DOT1L_HUMAN DOT1L_HUMAN] Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones. Binds to DNA. |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | A survey of the human genome was performed to understand the constituency of protein methyltransferases (PMTs; both protein arginine (PRMTs) and lysine (PKMTs) methyltransferases) and the relatedness of their catalytic domains. We identified 51 PKMT proteins based on similarity to the canonical SET-domain. DOT1L, a known PKMT, did not fit within the PKMT family, but did group with the PRMTs, along with 44 other proteins, including the METTL and NSUN proteins. We show that a representative METTL, METTL11A, demonstrates catalytic activity as a histone methyltransferase. We also solved the co-crystal structures of DOT1L with SAM and SAH bound in its active site. The conformation of both ligands is virtually identical to that found in known PRMTs, METTL and NSUN proteins, and is distinct from that seen in the SET domain PKMTs. We have developed biochemical assays for 11 members of the PMT target class and have profiled the affinity of three ligands for these enzymes: the common methyl-donating substrate S-adenosylmethionime (SAM); the common reaction product S-adenosylhomocysteine (SAH); and the natural product sinefungin. The affinity of each of these ligands is mapped onto the family trees of the PKMTs and PRMTs to reveal patterns of ligand recognition by these enzymes.
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| - | | + | |
| - | Chemogenetic Analysis of Human Protein Methyltransferases.,Richon VM, Johnston D, Sneeringer CJ, Jin L, Majer CR, Elliston K, Fred Jerva L, Scott MP, Copeland RA Chem Biol Drug Des. 2011 May 12. doi: 10.1111/j.1747-0285.2011.01135.x. PMID:21564555<ref>PMID:21564555</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3qox" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
| | *[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]] | | *[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]] |
| - | == References == | |
| - | <references/> | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Histone-lysine N-methyltransferase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Jin, L]] | + | [[Category: Jin L]] |
| - | [[Category: H3k79 methylation]]
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| - | [[Category: Transferase]]
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