3f9w: Difference between revisions

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-{{Seed}}
-[[Image:3f9w.png|left|200px]]
-<!--
+==Structural Insights into Lysine Multiple Methylation by SET Domain Methyltransferases, SET8-Y334F / H4-Lys20 / AdoHcy==
-The line below this paragraph, containing "STRUCTURE_3f9w", creates the "Structure Box" on the page.
+<StructureSection load='3f9w' size='340' side='right'caption='[[3f9w]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3f9w]] is a 8 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=3F9W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F9W FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</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>
-{{STRUCTURE_3f9w|  PDB=3f9w  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3f9w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f9w OCA], [https://pdbe.org/3f9w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f9w RCSB], [https://www.ebi.ac.uk/pdbsum/3f9w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f9w ProSAT]</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/f9/3f9w_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=3f9w ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+SET domain protein lysine methyltransferases (PKMTs) regulate transcription and other cellular functions through site-specific methylation of histones and other substrates. PKMTs catalyze the formation of monomethylated, dimethylated, or trimethylated products, establishing an additional hierarchy with respect to methyllysine recognition in signaling. Biochemical studies of PKMTs have identified a conserved position within their active sites, the Phe/Tyr switch, that governs their respective product specificities. To elucidate the mechanism underlying this switch, we have characterized a Phe/Tyr switch mutant of the histone H4 Lys-20 (H4K20) methyltransferase SET8, which alters its specificity from a monomethyltransferase to a dimethyltransferase. The crystal structures of the SET8 Y334F mutant bound to histone H4 peptides bearing unmodified, monomethyl, and dimethyl Lys-20 reveal that the phenylalanine substitution attenuates hydrogen bonding to a structurally conserved water molecule adjacent to the Phe/Tyr switch, facilitating its dissociation. The additional space generated by the solvent's dissociation enables the monomethyllysyl side chain to adopt a conformation that is catalytically competent for dimethylation and furnishes sufficient volume to accommodate the dimethyl epsilon-ammonium product. Collectively, these results indicate that the Phe/Tyr switch regulates product specificity through altering the affinity of an active-site water molecule whose dissociation is required for lysine multiple methylation.
-===Structural Insights into Lysine Multiple Methylation by SET Domain Methyltransferases, SET8-Y334F / H4-Lys20 / AdoHcy===
+Structural origins for the product specificity of SET domain protein methyltransferases.,Couture JF, Dirk LM, Brunzelle JS, Houtz RL, Trievel RC Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20659-64. Epub 2008 Dec 16. PMID:19088188<ref>PMID:19088188</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3f9w" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_19088188}}, adds the Publication Abstract to the page
+*[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 19088188 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_19088188}}
+__TOC__
+</StructureSection>
-==About this Structure==
-F9W is a 8 chains structure of sequences 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=3F9W OCA].
-==Reference==
-Structural origins for the product specificity of SET domain protein methyltransferases., Couture JF, Dirk LM, Brunzelle JS, Houtz RL, Trievel RC, Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20659-64. Epub 2008 Dec 16. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/19088188 19088188]
-[[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.A.]]
+[[Category: Couture J-F]]
-[[Category: Houtz, R L.]]
+[[Category: Dirk LMA]]
-[[Category: Trievel, R C.]]
+[[Category: Houtz RL]]
-[[Category: Acetylation]]
+[[Category: Trievel RC]]
-[[Category: Alternative splicing]]
-[[Category: Cell cycle]]
-[[Category: Cell division]]
-[[Category: Chromatin regulator]]
-[[Category: Chromosomal protein]]
-[[Category: Coiled coil]]
-[[Category: Dna-binding]]
-[[Category: Histone]]
-[[Category: Lysine]]
-[[Category: Methylation]]
-[[Category: Methyltransferase]]
-[[Category: Mitosis]]
-[[Category: Nucleosome core]]
-[[Category: Nucleus]]
-[[Category: Repressor]]
-[[Category: S-adenosyl-l-methionine]]
-[[Category: Set]]
-[[Category: Transcription]]
-[[Category: Transcription regulation]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 14 12:44:33 2009''