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2rfi

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Revision as of 10:53, 5 September 2018

Crystal structure of catalytic domain of human euchromatic histone methyltransferase 1 in complex with SAH and dimethylated H3K9 peptide

Structural highlights

2rfi is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Related:	2igq
Gene:	EHMT1, EUHMTASE1, KIAA1876 (HUMAN)
Activity:	Histone-lysine N-methyltransferase, with EC number 2.1.1.43
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[EHMT1_HUMAN] Defects in EHMT1 are the cause of chromosome 9q subtelomeric deletion syndrome (9q- syndrome) [MIM:610253]. Common features seen in these patients are severe mental retardation, hypotonia, brachy(micro)cephaly, epileptic seizures, flat face with hypertelorism, synophrys, anteverted nares, cupid bow or tented upper lip, everted lower lip, prognathism, macroglossia, conotruncal heart defects, and behavioral problems.

Function

[EHMT1_HUMAN] Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. During G0 phase, it probably contributes to silencing of MYC- and E2F-responsive genes, suggesting a role in G0/G1 transition in cell cycle. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53.^[1] ^[2]

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 methyltransferases deposit methyl marks on specific histone tail lysine residues and play a major role in epigenetic regulation of gene transcription. We solved the structures of the catalytic domains of GLP, G9a, Suv39H2 and PRDM2, four of the eight known human H3K9 methyltransferases in their apo conformation or in complex with the methyl donating cofactor, and peptide substrates. We analyzed the structural determinants for methylation state specificity, and designed a G9a mutant able to tri-methylate H3K9. We show that the I-SET domain acts as a rigid docking platform, while induced-fit of the Post-SET domain is necessary to achieve a catalytically competent conformation. We also propose a model where long-range electrostatics bring enzyme and histone substrate together, while the presence of an arginine upstream of the target lysine is critical for binding and specificity. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.

Structural biology of human H3K9 methyltransferases.,Wu H, Min J, Lunin VV, Antoshenko T, Dombrovski L, Zeng H, Allali-Hassani A, Campagna-Slater V, Vedadi M, Arrowsmith CH, Plotnikov AN, Schapira M PLoS One. 2010 Jan 11;5(1):e8570. PMID:20084102^[3]

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

References

↑ Ogawa H, Ishiguro K, Gaubatz S, Livingston DM, Nakatani Y. A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells. Science. 2002 May 10;296(5570):1132-6. PMID:12004135 doi:10.1126/science.1069861
↑ Huang J, Dorsey J, Chuikov S, Zhang X, Jenuwein T, Reinberg D, Berger SL. G9A and GLP methylate lysine 373 in the tumor suppressor p53. J Biol Chem. 2010 Jan 29. PMID:20118233 doi:M109.062588
↑ Wu H, Min J, Lunin VV, Antoshenko T, Dombrovski L, Zeng H, Allali-Hassani A, Campagna-Slater V, Vedadi M, Arrowsmith CH, Plotnikov AN, Schapira M. Structural biology of human H3K9 methyltransferases. PLoS One. 2010 Jan 11;5(1):e8570. PMID:20084102 doi:10.1371/journal.pone.0008570

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2rfi"

@@ Line 1: / Line 1: @@
 ==Crystal structure of catalytic domain of human euchromatic histone methyltransferase 1 in complex with SAH and dimethylated H3K9 peptide==
 <StructureSection load='2rfi' size='340' side='right' caption='[[2rfi]], [[Resolution|resolution]] 1.59&Aring;' scene=''>
@@ Line 8: / Line 9: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EHMT1, EUHMTASE1, KIAA1876 ([http://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'>[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=2rfi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rfi OCA], [http://pdbe.org/2rfi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2rfi RCSB], [http://www.ebi.ac.uk/pdbsum/2rfi PDBsum]</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=2rfi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rfi OCA], [http://pdbe.org/2rfi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2rfi RCSB], [http://www.ebi.ac.uk/pdbsum/2rfi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2rfi ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 18: / Line 19: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rf/2rfi_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rf/2rfi_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 52: / Line 53: @@
 [[Category: Weigelt, J]]
 [[Category: Wu, H]]
+[[Category: Acetylation]]
+[[Category: Alternative splicing]]
 [[Category: Ank repeat]]
 [[Category: Chromatin regulator]]
@@ Line 63: / Line 66: @@
 [[Category: Nucleus]]
 [[Category: Phosphorylation]]
+[[Category: Polymorphism]]
 [[Category: S-adenosyl-l-methionine]]
 [[Category: Sgc]]
 [[Category: Transferase]]

2rfi

From Proteopedia

Revision as of 10:53, 5 September 2018

Crystal structure of catalytic domain of human euchromatic histone methyltransferase 1 in complex with SAH and dimethylated H3K9 peptide

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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