2bqz

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of a ternary complex of the human histone methyltransferase Pr-SET7 (also known as SET8)

Structural highlights

2bqz 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 1.5Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KMT5A_HUMAN Protein-lysine N-methyltransferase that monomethylates both histones and non-histone proteins. Specifically monomethylates 'Lys-20' of histone H4 (H4K20me1). H4K20me1 is enriched during mitosis and represents a specific tag for epigenetic transcriptional repression. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. Required for cell proliferation, probably by contributing to the maintenance of proper higher-order structure of DNA during mitosis. Involved in chromosome condensation and proper cytokinesis. Nucleosomes are preferred as substrate compared to free histones. Mediates monomethylation of p53/TP53 at 'Lys-382', leading to repress p53/TP53-target genes. Plays a negative role in TGF-beta response regulation and a positive role in cell migration.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8]

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

Methylation of lysine residues of histones is an important epigenetic mark that correlates with functionally distinct regions of chromatin. We present here the crystal structure of a ternary complex of the enzyme Pr-Set7 (also known as Set8) that methylates Lys 20 of histone H4 (H4-K20). We show that the enzyme is exclusively a mono-methylase and is therefore responsible for a signaling role quite distinct from that established by other enzymes that target this histone residue. We provide evidence from NMR for the C-flanking domains of SET proteins becoming ordered upon addition of AdoMet cofactor and develop a model for the catalytic cycle of these enzymes. The crystal structure reveals the basis of the specificity of the enzyme for H4-K20 because a histidine residue within the substrate, close to the target lysine, is required for completion of the active site. We also show how a highly variable component of the SET domain is responsible for many of the enzymes' interactions with its target histone peptide and probably also how this part of the structure ensures that Pr-Set7 is nucleosome specific.

Specificity and mechanism of the histone methyltransferase Pr-Set7.,Xiao B, Jing C, Kelly G, Walker PA, Muskett FW, Frenkiel TA, Martin SR, Sarma K, Reinberg D, Gamblin SJ, Wilson JR Genes Dev. 2005 Jun 15;19(12):1444-54. Epub 2005 Jun 2. PMID:15933069^[9]

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

References

↑ Nishioka K, Rice JC, Sarma K, Erdjument-Bromage H, Werner J, Wang Y, Chuikov S, Valenzuela P, Tempst P, Steward R, Lis JT, Allis CD, Reinberg D. PR-Set7 is a nucleosome-specific methyltransferase that modifies lysine 20 of histone H4 and is associated with silent chromatin. Mol Cell. 2002 Jun;9(6):1201-13. PMID:12086618
↑ Fang J, Feng Q, Ketel CS, Wang H, Cao R, Xia L, Erdjument-Bromage H, Tempst P, Simon JA, Zhang Y. Purification and functional characterization of SET8, a nucleosomal histone H4-lysine 20-specific methyltransferase. Curr Biol. 2002 Jul 9;12(13):1086-99. PMID:12121615
↑ Julien E, Herr W. A switch in mitotic histone H4 lysine 20 methylation status is linked to M phase defects upon loss of HCF-1. Mol Cell. 2004 Jun 18;14(6):713-25. PMID:15200950 doi:http://dx.doi.org/10.1016/j.molcel.2004.06.008
↑ Xiao B, Jing C, Kelly G, Walker PA, Muskett FW, Frenkiel TA, Martin SR, Sarma K, Reinberg D, Gamblin SJ, Wilson JR. Specificity and mechanism of the histone methyltransferase Pr-Set7. Genes Dev. 2005 Jun 15;19(12):1444-54. Epub 2005 Jun 2. PMID:15933069 doi:http://dx.doi.org/10.1101/gad.1315905
↑ Couture JF, Collazo E, Brunzelle JS, Trievel RC. Structural and functional analysis of SET8, a histone H4 Lys-20 methyltransferase. Genes Dev. 2005 Jun 15;19(12):1455-65. Epub 2005 Jun 2. PMID:15933070 doi:10.1101/gad.1318405
↑ Sims JK, Houston SI, Magazinnik T, Rice JC. A trans-tail histone code defined by monomethylated H4 Lys-20 and H3 Lys-9 demarcates distinct regions of silent chromatin. J Biol Chem. 2006 May 5;281(18):12760-6. Epub 2006 Mar 3. PMID:16517599 doi:http://dx.doi.org/10.1074/jbc.M513462200
↑ Shi X, Kachirskaia I, Yamaguchi H, West LE, Wen H, Wang EW, Dutta S, Appella E, Gozani O. Modulation of p53 function by SET8-mediated methylation at lysine 382. Mol Cell. 2007 Aug 17;27(4):636-46. PMID:17707234 doi:http://dx.doi.org/10.1016/j.molcel.2007.07.012
↑ Abbas T, Mueller AC, Shibata E, Keaton M, Rossi M, Dutta A. CRL1-FBXO11 promotes Cdt2 ubiquitylation and degradation and regulates Pr-Set7/Set8-mediated cellular migration. Mol Cell. 2013 Mar 28;49(6):1147-58. doi: 10.1016/j.molcel.2013.02.003. Epub 2013, Mar 7. PMID:23478445 doi:http://dx.doi.org/10.1016/j.molcel.2013.02.003
↑ Xiao B, Jing C, Kelly G, Walker PA, Muskett FW, Frenkiel TA, Martin SR, Sarma K, Reinberg D, Gamblin SJ, Wilson JR. Specificity and mechanism of the histone methyltransferase Pr-Set7. Genes Dev. 2005 Jun 15;19(12):1444-54. Epub 2005 Jun 2. PMID:15933069 doi:http://dx.doi.org/10.1101/gad.1315905

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/2bqz"

@@ Line 1: / Line 1: @@
-==CRYSTAL STRUCTURE OF A TERNARY COMPLEX OF THE HUMAN HISTONE METHYLTRANSFERASE PR-SET7 (ALSO KNOWN AS SET8)==
-<StructureSection load='2bqz' size='340' side='right' caption='[[2bqz]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
+==Crystal structure of a ternary complex of the human histone methyltransferase Pr-SET7 (also known as SET8)==
+<StructureSection load='2bqz' size='340' side='right'caption='[[2bqz]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2bqz]] is a 4 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=2BQZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BQZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2bqz]] 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=2BQZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BQZ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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]] 1.5&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MLZ:N-METHYL-LYSINE'>MLZ</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLZ:N-METHYL-LYSINE'>MLZ</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=2bqz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bqz OCA], [https://pdbe.org/2bqz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bqz RCSB], [https://www.ebi.ac.uk/pdbsum/2bqz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bqz 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=2bqz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bqz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2bqz RCSB], [http://www.ebi.ac.uk/pdbsum/2bqz PDBsum]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/KMT5A_HUMAN KMT5A_HUMAN] Protein-lysine N-methyltransferase that monomethylates both histones and non-histone proteins. Specifically monomethylates 'Lys-20' of histone H4 (H4K20me1). H4K20me1 is enriched during mitosis and represents a specific tag for epigenetic transcriptional repression. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. Required for cell proliferation, probably by contributing to the maintenance of proper higher-order structure of DNA during mitosis. Involved in chromosome condensation and proper cytokinesis. Nucleosomes are preferred as substrate compared to free histones. Mediates monomethylation of p53/TP53 at 'Lys-382', leading to repress p53/TP53-target genes. Plays a negative role in TGF-beta response regulation and a positive role in cell migration.<ref>PMID:12086618</ref> <ref>PMID:12121615</ref> <ref>PMID:15200950</ref> <ref>PMID:15933069</ref> <ref>PMID:15933070</ref> <ref>PMID:16517599</ref> <ref>PMID:17707234</ref> <ref>PMID:23478445</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/bq/2bqz_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bq/2bqz_consurf.spt"</scriptWhenChecked>
-    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2bqz ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 26: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2bqz" 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: Frenkiel, T A]]
+[[Category: Large Structures]]
-[[Category: Gamblin, S J]]
+[[Category: Frenkiel TA]]
-[[Category: Jing, C]]
+[[Category: Gamblin SJ]]
-[[Category: Kelly, G]]
+[[Category: Jing C]]
-[[Category: Martin, S R]]
+[[Category: Kelly G]]
-[[Category: Muskett, F W]]
+[[Category: Martin SR]]
-[[Category: Reinberg, D]]
+[[Category: Muskett FW]]
-[[Category: Sarma, K]]
+[[Category: Reinberg D]]
-[[Category: Walker, P A]]
+[[Category: Sarma K]]
-[[Category: Wilson, J R]]
+[[Category: Walker PA]]
-[[Category: Xiao, B]]
+[[Category: Wilson JR]]
-[[Category: Histone h4 methyltransfersae]]
+[[Category: Xiao B]]
-[[Category: Lysine methyltransferase]]
-[[Category: Set domain]]
-[[Category: Transferase]]

2bqz

From Proteopedia

Current revision

Crystal structure of a ternary complex of the human histone methyltransferase Pr-SET7 (also known as SET8)

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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