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3m59

From Proteopedia

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SET7/9 Y245A in complex with TAF10-K189me2 peptide and AdoHcy

Structural highlights

3m59 is a 2 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 1.7Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

SET domain lysine methyltransferases (KMTs) methylate specific lysine residues in histone and non-histone substrates. These enzymes also display product specificity by catalyzing distinct degrees of methylation of the lysine epsilon-amino group. To elucidate the molecular mechanism underlying this specificity, we have characterized the Y245A and Y305F mutants of the human KMT SET7/9 (also known as KMT7) that alter its product specificity from a monomethyltransferase to a di- and a trimethyltransferase, respectively. Crystal structures of these mutants in complex with peptides bearing unmodified, mono-, di-, and trimethylated lysines illustrate the roles of active site water molecules in aligning the lysine epsilon-amino group for methyl transfer with S-adenosylmethionine. Displacement or dissociation of these solvent molecules enlarges the diameter of the active site, accommodating the increasing size of the methylated epsilon-amino group during successive methyl transfer reactions. Together, these results furnish new insights into the roles of active site water molecules in modulating lysine multiple methylation by SET domain KMTs and provide the first molecular snapshots of the mono-, di-, and trimethyl transfer reactions catalyzed by these enzymes.

SET7/9 catalytic mutants reveal the role of active site water molecules in lysine multiple methylation.,Del Rizzo PA, Couture JF, Dirk LM, Strunk BS, Roiko MS, Brunzelle JS, Houtz RL, Trievel RC J Biol Chem. 2010 Oct 8;285(41):31849-58. Epub 2010 Aug 1. PMID:20675860^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Martens JH, Verlaan M, Kalkhoven E, Zantema A. Cascade of distinct histone modifications during collagenase gene activation. Mol Cell Biol. 2003 Mar;23(5):1808-16. PMID:12588998
↑ Kouskouti A, Scheer E, Staub A, Tora L, Talianidis I. Gene-specific modulation of TAF10 function by SET9-mediated methylation. Mol Cell. 2004 Apr 23;14(2):175-82. PMID:15099517
↑ Francis J, Chakrabarti SK, Garmey JC, Mirmira RG. Pdx-1 links histone H3-Lys-4 methylation to RNA polymerase II elongation during activation of insulin transcription. J Biol Chem. 2005 Oct 28;280(43):36244-53. Epub 2005 Sep 1. PMID:16141209 doi:M505741200
↑ Huang J, Perez-Burgos L, Placek BJ, Sengupta R, Richter M, Dorsey JA, Kubicek S, Opravil S, Jenuwein T, Berger SL. Repression of p53 activity by Smyd2-mediated methylation. Nature. 2006 Nov 30;444(7119):629-32. Epub 2006 Nov 15. PMID:17108971 doi:10.1038/nature05287
↑ Xiao B, Jing C, Wilson JR, Walker PA, Vasisht N, Kelly G, Howell S, Taylor IA, Blackburn GM, Gamblin SJ. Structure and catalytic mechanism of the human histone methyltransferase SET7/9. Nature. 2003 Feb 6;421(6923):652-6. Epub 2003 Jan 22. PMID:12540855 doi:10.1038/nature01378
↑ Chuikov S, Kurash JK, Wilson JR, Xiao B, Justin N, Ivanov GS, McKinney K, Tempst P, Prives C, Gamblin SJ, Barlev NA, Reinberg D. Regulation of p53 activity through lysine methylation. Nature. 2004 Nov 18;432(7015):353-60. Epub 2004 Nov 3. PMID:15525938 doi:10.1038/nature03117
↑ Del Rizzo PA, Couture JF, Dirk LM, Strunk BS, Roiko MS, Brunzelle JS, Houtz RL, Trievel RC. SET7/9 catalytic mutants reveal the role of active site water molecules in lysine multiple methylation. J Biol Chem. 2010 Oct 8;285(41):31849-58. Epub 2010 Aug 1. PMID:20675860 doi:http://dx.doi.org/10.1074/jbc.M110.114587

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3m59"

@@ Line 1: / Line 1: @@
 ==SET7/9 Y245A in complex with TAF10-K189me2 peptide and AdoHcy==
-<StructureSection load='3m59' size='340' side='right' caption='[[3m59]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+<StructureSection load='3m59' size='340' side='right'caption='[[3m59]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3m59]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3M59 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3M59 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3m59]] is a 2 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=3M59 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3M59 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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]] 1.7&#8491;</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=MLY:N-DIMETHYL-LYSINE'>MLY</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2f69|2f69]], [[3m54|3m54]], [[3m55|3m55]], [[3m56|3m56]], [[3m57|3m57]], [[3m58|3m58]], [[3m53|3m53]], [[3m5a|3m5a]]</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=3m59 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3m59 OCA], [https://pdbe.org/3m59 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3m59 RCSB], [https://www.ebi.ac.uk/pdbsum/3m59 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3m59 ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KIAA1717, KMT7, SET7, SET9, SETD7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3m59 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3m59 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3m59 RCSB], [http://www.ebi.ac.uk/pdbsum/3m59 PDBsum]</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/m5/3m59_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/m5/3m59_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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=3m59 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 28: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3m59" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Histone methyltransferase|Histone methyltransferase]]
+*[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Histone-lysine N-methyltransferase]]
 [[Category: Homo sapiens]]
-[[Category: Brunzelle, J S]]
+[[Category: Large Structures]]
-[[Category: Couture, J F]]
+[[Category: Brunzelle JS]]
-[[Category: Dirk, L M]]
+[[Category: Couture J-F]]
-[[Category: Houtz, R L]]
+[[Category: Del Rizzo PA]]
-[[Category: Rizzo, P A.Del]]
+[[Category: Dirk LM]]
-[[Category: Roiko, M S]]
+[[Category: Houtz RL]]
-[[Category: Strunk, B S]]
+[[Category: Roiko MS]]
-[[Category: Trievel, R C]]
+[[Category: Strunk BS]]
-[[Category: Chromatin regulator]]
+[[Category: Trievel RC]]
-[[Category: Chromosomal protein]]
-[[Category: Methyltransferase]]
-[[Category: N-dimethyllysine]]
-[[Category: Nucleus]]
-[[Category: S-adenosyl-l-homocysteine]]
-[[Category: S-adenosyl-l-methionine]]
-[[Category: Set domain]]
-[[Category: Taf10 peptide]]
-[[Category: Ternary complex]]
-[[Category: Transcription]]
-[[Category: Transcription regulation]]
-[[Category: Transferase]]

3m59

From Proteopedia

Current revision

SET7/9 Y245A in complex with TAF10-K189me2 peptide and AdoHcy

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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