View source for 2f69


==Ternary complex of SET7/9 bound to AdoHcy and a TAF10 peptide==
<StructureSection load='2f69' size='340' side='right'caption='[[2f69]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2f69]] is a 2 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=2F69 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2F69 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></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=MLZ:N-METHYL-LYSINE'>MLZ</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SET7, KIAA1717 ([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=2f69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f69 OCA], [https://pdbe.org/2f69 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2f69 RCSB], [https://www.ebi.ac.uk/pdbsum/2f69 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2f69 ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/SETD7_HUMAN SETD7_HUMAN]] Histone methyltransferase that specifically monomethylates 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Plays a central role in the transcriptional activation of genes such as collagenase or insulin. Recruited by IPF1/PDX-1 to the insulin promoter, leading to activate transcription. Has also methyltransferase activity toward non-histone proteins such as p53/TP53, TAF10, and possibly TAF7 by recognizing and binding the [KR]-[STA]-K in substrate proteins. Monomethylates 'Lys-189' of TAF10, leading to increase the affinity of TAF10 for RNA polymerase II. Monomethylates 'Lys-372' of p53/TP53, stabilizing p53/TP53 and increasing p53/TP53-mediated transcriptional activation.<ref>PMID:12588998</ref> <ref>PMID:15099517</ref> <ref>PMID:16141209</ref> <ref>PMID:17108971</ref> <ref>PMID:12540855</ref> <ref>PMID:15525938</ref>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f6/2f69_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2f69 ConSurf].
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== Publication Abstract from PubMed ==
Human SET7/9 is a protein lysine methyltransferase (PKMT) that methylates histone H3, the tumor suppressor p53 and the TBP-associated factor TAF10. To elucidate the determinants of its substrate specificity, we have solved the enzyme's structure bound to a TAF10 peptide and examined its ability to methylate histone H3, TAF10 and p53 substrates bearing either mutations or covalent modifications within their respective methylation sites. Collectively, our data reveal that SET7/9 recognizes a conserved K/R-S/T/A motif preceding the lysine substrate and has a propensity to bind aspartates and asparagines on the C-terminal side of the lysine target. We then used a sequence-based approach with this motif to identify novel substrates for this PKMT. Among the putative targets is TAF7, which is methylated at Lys5 by the enzyme in vitro. These results demonstrate the predictive value of the consensus motif in identifying novel substrates for SET7/9.

Structural basis for the methylation site specificity of SET7/9.,Couture JF, Collazo E, Hauk G, Trievel RC Nat Struct Mol Biol. 2006 Feb;13(2):140-6. Epub 2006 Jan 15. PMID:16415881<ref>PMID:16415881</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2f69" style="background-color:#fffaf0;"></div>

==See Also==
*[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Histone-lysine N-methyltransferase]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Collazo, E]]
[[Category: Couture, J F]]
[[Category: Hauk, G]]
[[Category: Trievel, R C]]
[[Category: Enzyme-peptide-adohcy complex]]
[[Category: Protein lysine methyltransferase]]
[[Category: Set domain]]
[[Category: Transferase]]