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| - | [[Image:1u2z.gif|left|200px]]<br /><applet load="1u2z" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1u2z, resolution 2.20Å" /> | |
| - | '''Crystal structure of histone K79 methyltransferase Dot1p from yeast'''<br /> | |
| | | | |
| - | ==Overview== | + | ==Crystal structure of histone K79 methyltransferase Dot1p from yeast== |
| - | Methylation of Lys79 on histone H3 by Dot1p is important for gene, silencing. The elongated structure of the conserved core of yeast Dot1p, contains an N-terminal helical domain and a seven-stranded catalytic, domain that harbors the binding site for the methyl-donor and an active, site pocket sided with conserved hydrophobic residues. The, S-adenosyl-L-homocysteine exhibits an extended conformation distinct from, the folded conformation observed in structures of SET domain histone, lysine methyltransferases. A catalytic asparagine (Asn479), located at the, bottom of the active site pocket, suggests a mechanism similar to that, employed for amino methylation in DNA and protein glutamine methylation., The acidic, concave cleft between the two domains contains two basic, residue binding pockets that could accommodate the outwardly protruding, basic side chains around Lys79 of histone H3 on the disk-like nucleosome, surface. Biochemical studies suggest that recombinant Dot1 proteins are, active on recombinant nucleosomes, free of any modifications.
| + | <StructureSection load='1u2z' size='340' side='right'caption='[[1u2z]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1u2z]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U2Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1U2Z 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]] 2.2Å</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> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1u2z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u2z OCA], [https://pdbe.org/1u2z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1u2z RCSB], [https://www.ebi.ac.uk/pdbsum/1u2z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1u2z ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/DOT1_YEAST DOT1_YEAST] Histone methyltransferase that specifically methylates histone H3 to form H3K79me. This methylation is required for telomere silencing and for the pachytene checkpoint during the meiotic cell cycle by allowing the recruitment of RAD9 to double strand breaks. Nucleosomes are preferred as substrate compared to free histones. Can bind to DNA (in vitro).<ref>PMID:9755194</ref> <ref>PMID:11029058</ref> <ref>PMID:12097318</ref> <ref>PMID:12152067</ref> <ref>PMID:12574507</ref> <ref>PMID:15632126</ref> <ref>PMID:16166626</ref> <ref>PMID:15292170</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/u2/1u2z_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=1u2z ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | ==About this Structure== | + | ==See Also== |
| - | 1U2Z is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with SAH as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1U2Z OCA].
| + | *[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]] |
| - | | + | == References == |
| - | ==Reference== | + | <references/> |
| - | Structure of the conserved core of the yeast Dot1p, a nucleosomal histone H3 lysine 79 methyltransferase., Sawada K, Yang Z, Horton JR, Collins RE, Zhang X, Cheng X, J Biol Chem. 2004 Oct 8;279(41):43296-306. Epub 2004 Jul 29. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15292170 15292170]
| + | __TOC__ |
| - | [[Category: Histone-lysine N-methyltransferase]] | + | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Saccharomyces cerevisiae]] | | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Single protein]]
| + | [[Category: Cheng X]] |
| - | [[Category: Cheng, X.]] | + | [[Category: Collins RE]] |
| - | [[Category: Collins, R.E.]] | + | [[Category: Horton JR]] |
| - | [[Category: Horton, J.R.]] | + | [[Category: Sawada K]] |
| - | [[Category: Sawada, K.]] | + | [[Category: Yang Z]] |
| - | [[Category: Yang, Z.]] | + | [[Category: Zhang X]] |
| - | [[Category: Zhang, X.]] | + | |
| - | [[Category: SAH]]
| + | |
| - | [[Category: histone methyltransferase]]
| + | |
| - | [[Category: nucleosome]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 03:48:48 2007''
| + | |
| Structural highlights
Function
DOT1_YEAST Histone methyltransferase that specifically methylates histone H3 to form H3K79me. This methylation is required for telomere silencing and for the pachytene checkpoint during the meiotic cell cycle by allowing the recruitment of RAD9 to double strand breaks. Nucleosomes are preferred as substrate compared to free histones. Can bind to DNA (in vitro).[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.
See Also
References
- ↑ Singer MS, Kahana A, Wolf AJ, Meisinger LL, Peterson SE, Goggin C, Mahowald M, Gottschling DE. Identification of high-copy disruptors of telomeric silencing in Saccharomyces cerevisiae. Genetics. 1998 Oct;150(2):613-32. PMID:9755194
- ↑ San-Segundo PA, Roeder GS. Role for the silencing protein Dot1 in meiotic checkpoint control. Mol Biol Cell. 2000 Oct;11(10):3601-15. PMID:11029058
- ↑ Lacoste N, Utley RT, Hunter JM, Poirier GG, Cote J. Disruptor of telomeric silencing-1 is a chromatin-specific histone H3 methyltransferase. J Biol Chem. 2002 Aug 23;277(34):30421-4. Epub 2002 Jul 3. PMID:12097318 doi:http://dx.doi.org/10.1074/jbc.C200366200
- ↑ Briggs SD, Xiao T, Sun ZW, Caldwell JA, Shabanowitz J, Hunt DF, Allis CD, Strahl BD. Gene silencing: trans-histone regulatory pathway in chromatin. Nature. 2002 Aug 1;418(6897):498. Epub 2002 Jul 14. PMID:12152067 doi:10.1038/nature00970
- ↑ Ng HH, Ciccone DN, Morshead KB, Oettinger MA, Struhl K. Lysine-79 of histone H3 is hypomethylated at silenced loci in yeast and mammalian cells: a potential mechanism for position-effect variegation. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1820-5. Epub 2003 Feb 6. PMID:12574507 doi:http://dx.doi.org/10.1073/pnas.0437846100
- ↑ Giannattasio M, Lazzaro F, Plevani P, Muzi-Falconi M. The DNA damage checkpoint response requires histone H2B ubiquitination by Rad6-Bre1 and H3 methylation by Dot1. J Biol Chem. 2005 Mar 18;280(11):9879-86. Epub 2005 Jan 4. PMID:15632126 doi:M414453200
- ↑ Wysocki R, Javaheri A, Allard S, Sha F, Cote J, Kron SJ. Role of Dot1-dependent histone H3 methylation in G1 and S phase DNA damage checkpoint functions of Rad9. Mol Cell Biol. 2005 Oct;25(19):8430-43. PMID:16166626 doi:http://dx.doi.org/25/19/8430
- ↑ Sawada K, Yang Z, Horton JR, Collins RE, Zhang X, Cheng X. Structure of the conserved core of the yeast Dot1p, a nucleosomal histone H3 lysine 79 methyltransferase. J Biol Chem. 2004 Oct 8;279(41):43296-306. Epub 2004 Jul 29. PMID:15292170 doi:10.1074/jbc.M405902200
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