3epz

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{{STRUCTURE_3epz| PDB=3epz | SCENE= }}
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==Structure of the replication foci-targeting sequence of human DNA cytosine methyltransferase DNMT1==
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===Structure of the replication foci-targeting sequence of human DNA cytosine methyltransferase DNMT1===
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<StructureSection load='3epz' size='340' side='right' caption='[[3epz]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
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{{ABSTRACT_PUBMED_21389349}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3epz]] 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=3EPZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3EPZ FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AIM, CXX9, CXXC9, DNMT, DNMT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_(cytosine-5-)-methyltransferase DNA (cytosine-5-)-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.37 2.1.1.37] </span></td></tr>
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<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=3epz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3epz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3epz RCSB], [http://www.ebi.ac.uk/pdbsum/3epz PDBsum]</span></td></tr>
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</table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/DNMT1_HUMAN DNMT1_HUMAN]] Defects in DNMT1 are the cause of hereditary sensory neuropathy type 1E (HSN1E) [MIM:[http://omim.org/entry/614116 614116]]. A neurodegenerative disorder characterized by adult onset of progressive peripheral sensory loss associated with progressive hearing impairment and early-onset dementia.<ref>PMID:21532572</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/DNMT1_HUMAN DNMT1_HUMAN]] Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In association with DNMT3B and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9.<ref>PMID:16357870</ref> <ref>PMID:18754681</ref> <ref>PMID:18413740</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ep/3epz_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Dnmt1 (DNA methyltransferase 1) is the principal enzyme responsible for maintenance of cytosine methylation at CpG dinucleotides in the mammalian genome. The N-terminal replication focus targeting sequence (RFTS) domain of Dnmt1 has been implicated in subcellular localization, protein association, and catalytic function. However, progress in understanding its function has been limited by the lack of assays for and a structure of this domain. Here, we show that the naked DNA- and polynucleosome-binding activities of Dnmt1 are inhibited by the RFTS domain, which functions by virtue of binding the catalytic domain to the exclusion of DNA. Kinetic analysis with a fluorogenic DNA substrate established the RFTS domain as a 600-fold inhibitor of Dnmt1 enzymatic activity. The crystal structure of the RFTS domain reveals a novel fold and supports a mechanism in which an RFTS-targeted Dnmt1-binding protein, such as Uhrf1, may activate Dnmt1 for DNA binding.
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==Disease==
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The replication focus targeting sequence (RFTS) domain is a DNA-competitive inhibitor of Dnmt1.,Syeda F, Fagan RL, Wean M, Avvakumov GV, Walker JR, Xue S, Dhe-Paganon S, Brenner C J Biol Chem. 2011 Apr 29;286(17):15344-51. Epub 2011 Mar 9. PMID:21389349<ref>PMID:21389349</ref>
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[[http://www.uniprot.org/uniprot/DNMT1_HUMAN DNMT1_HUMAN]] Defects in DNMT1 are the cause of hereditary sensory neuropathy type 1E (HSN1E) [MIM:[http://omim.org/entry/614116 614116]]. A neurodegenerative disorder characterized by adult onset of progressive peripheral sensory loss associated with progressive hearing impairment and early-onset dementia.<ref>PMID:21532572</ref>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://www.uniprot.org/uniprot/DNMT1_HUMAN DNMT1_HUMAN]] Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In association with DNMT3B and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9.<ref>PMID:16357870</ref><ref>PMID:18754681</ref><ref>PMID:18413740</ref>
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</div>
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==About this Structure==
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[[3epz]] 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=3EPZ OCA].
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==See Also==
==See Also==
*[[DNA methyltransferase|DNA methyltransferase]]
*[[DNA methyltransferase|DNA methyltransferase]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:021389349</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Arrowsmith, C H.]]
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[[Category: Arrowsmith, C H]]
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[[Category: Avvakumov, G V.]]
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[[Category: Avvakumov, G V]]
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[[Category: Bochkarev, A.]]
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[[Category: Bochkarev, A]]
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[[Category: Bountra, C.]]
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[[Category: Bountra, C]]
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[[Category: Dhe-Paganon, S.]]
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[[Category: Dhe-Paganon, S]]
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[[Category: Edwards, A M.]]
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[[Category: Edwards, A M]]
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[[Category: Li, Y.]]
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[[Category: Li, Y]]
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[[Category: SGC, Structural Genomics Consortium.]]
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[[Category: Structural genomic]]
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[[Category: Walker, J R.]]
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[[Category: Walker, J R]]
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[[Category: Weigelt, J.]]
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[[Category: Weigelt, J]]
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[[Category: Xue, S.]]
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[[Category: Xue, S]]
[[Category: Cell cycle]]
[[Category: Cell cycle]]
[[Category: Chromatin]]
[[Category: Chromatin]]
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[[Category: Sgc]]
[[Category: Sgc]]
[[Category: Sh3-like barrel]]
[[Category: Sh3-like barrel]]
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[[Category: Structural genomic]]
 
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[[Category: Structural genomics consortium]]
 
[[Category: Transcription]]
[[Category: Transcription]]
[[Category: Transcription regulation]]
[[Category: Transcription regulation]]

Revision as of 14:06, 18 December 2014

Structure of the replication foci-targeting sequence of human DNA cytosine methyltransferase DNMT1

3epz, resolution 2.31Å

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