3vv0: Difference between revisions
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The | ==Crystal structure of histone methyltransferase SET7/9 in complex with DAAM-3== | ||
<StructureSection load='3vv0' size='340' side='right'caption='[[3vv0]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3vv0]] 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=3VV0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VV0 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]] 2.001Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KH3:5-{[(3S)-3-AMINO-3-CARBOXYPROPYL][2-(HEXYLAMINO)ETHYL]AMINO}-5-DEOXYADENOSINE'>KH3</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=3vv0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vv0 OCA], [https://pdbe.org/3vv0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vv0 RCSB], [https://www.ebi.ac.uk/pdbsum/3vv0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vv0 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> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
SET7/9 is a protein lysine methyltransferase that methylates histone H3 and nonhistone proteins such as p53, TAF10 and oestrogen receptor alpha. In previous work, novel inhibitors of SET7/9 that are amine analogues of the coenzyme S-(5'-adenosyl)-L-methionine (AdoMet) have been developed. Here, crystal structures of SET7/9 are reported in complexes with two AdoMet analogues, designated DAAM-3 and AAM-1, in which an n-hexylaminoethyl group or an n-hexyl group is attached to the N atom that replaces the S atom of AdoMet, respectively. In both structures, the inhibitors bind to the coenzyme-binding site and their additional alkyl chain binds in the lysine-access channel. The N atom in the azaalkyl chain of DAAM-3 is located at almost the same position as the N-methyl C atom of the methylated lysine side chain in the substrate-peptide complex structures and stabilizes complex formation by hydrogen bonding to the substrate-binding site residues of SET7/9. On the other hand, the alkyl chain of AAM-1, which is a weaker inhibitor than DAAM-3, binds in the lysine-access channel only through hydrophobic and van der Waals interactions. Unexpectedly, the substrate-binding site of SET7/9 complexed with AAM-1 specifically interacts with the artificial N-terminal sequence of an adjacent symmetry-related molecule, presumably stabilizing the alkyl chain of AAM-1. | |||
Structures of histone methyltransferase SET7/9 in complexes with adenosylmethionine derivatives.,Niwa H, Handa N, Tomabechi Y, Honda K, Toyama M, Ohsawa N, Shirouzu M, Kagechika H, Hirano T, Umehara T, Yokoyama S Acta Crystallogr D Biol Crystallogr. 2013 Apr;69(Pt 4):595-602. doi:, 10.1107/S0907444912052092. Epub 2013 Mar 14. PMID:23519668<ref>PMID:23519668</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3vv0" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Handa N]] | |||
[[Category: Hirano T]] | |||
[[Category: Honda K]] | |||
[[Category: Kagechika H]] | |||
[[Category: Niwa H]] | |||
[[Category: Ohsawa N]] | |||
[[Category: Shirouzu M]] | |||
[[Category: Tomabechi Y]] | |||
[[Category: Toyama M]] | |||
[[Category: Umehara T]] | |||
[[Category: Yokoyama S]] | |||
