4ew4

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==mouse MBD4 glycosylase domain in complex with DNA containing a ribose sugar==
==mouse MBD4 glycosylase domain in complex with DNA containing a ribose sugar==
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<StructureSection load='4ew4' size='340' side='right' caption='[[4ew4]], [[Resolution|resolution]] 2.79&Aring;' scene=''>
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<StructureSection load='4ew4' size='340' side='right'caption='[[4ew4]], [[Resolution|resolution]] 2.79&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4ew4]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EW4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EW4 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4ew4]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EW4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EW4 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=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.791&#8491;</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=3DR:1,2-DIDEOXYRIBOFURANOSE-5-PHOSPHATE'>3DR</scene></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3DR:1,2-DIDEOXYRIBOFURANOSE-5-PHOSPHATE'>3DR</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ngn|1ngn]], [[4evv|4evv]], [[4ew0|4ew0]]</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ew4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ew4 OCA], [https://pdbe.org/4ew4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ew4 RCSB], [https://www.ebi.ac.uk/pdbsum/4ew4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ew4 ProSAT]</span></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Mbd4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</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=4ew4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ew4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ew4 RCSB], [http://www.ebi.ac.uk/pdbsum/4ew4 PDBsum]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/MBD4_MOUSE MBD4_MOUSE] Mismatch-specific DNA N-glycosylase involved in DNA repair. Has thymine glycosylase activity and is specific for G:T mismatches within methylated and unmethylated CpG sites. Can also remove uracil or 5-fluorouracil in G:U mismatches. Has no lyase activity. Was first identified as methyl-CpG-binding protein.
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The mammalian DNA glycosylase-methyl-CpG binding domain protein 4 (MBD4)-is involved in active DNA demethylation via the base excision repair pathway. MBD4 contains an N-terminal MBD and a C-terminal DNA glycosylase domain. MBD4 can excise the mismatched base paired with a guanine (G:X), where X is uracil, thymine or 5-hydroxymethyluracil (5hmU). These are, respectively, the deamination products of cytosine, 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). Here, we present three structures of the MBD4 C-terminal glycosylase domain (wild-type and its catalytic mutant D534N), in complex with DNA containing a G:T or G:5hmU mismatch. MBD4 flips the target nucleotide from the double-stranded DNA. The catalytic mutant D534N captures the intact target nucleotide in the active site binding pocket. MBD4 specifically recognizes the Watson-Crick polar edge of thymine or 5hmU via the O(2), N(3) and O(4) atoms, thus restricting its activity to thymine/uracil-based modifications while excluding cytosine and its derivatives. The wild-type enzyme cleaves the N-glycosidic bond, leaving the ribose ring in the flipped state, while the cleaved base is released. Unexpectedly, the C(1)' of the sugar has yet to be hydrolyzed and appears to form a stable intermediate with one of the side chain carboxyl oxygen atoms of D534, via either electrostatic or covalent interaction, suggesting a different catalytic mechanism from those of other DNA glycosylases.
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Excision of thymine and 5-hydroxymethyluracil by the MBD4 DNA glycosylase domain: structural basis and implications for active DNA demethylation.,Hashimoto H, Zhang X, Cheng X Nucleic Acids Res. 2012 Jun 27. PMID:22740654<ref>PMID:22740654</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==See Also==
==See Also==
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*[[Methyl CpG binding protein|Methyl CpG binding protein]]
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*[[Methyl CpG binding protein 3D structures|Methyl CpG binding protein 3D structures]]
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Cheng, X]]
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[[Category: Synthetic construct]]
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[[Category: Hashimoto, H]]
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[[Category: Cheng X]]
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[[Category: Zhang, X]]
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[[Category: Hashimoto H]]
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[[Category: Dna glycosylase]]
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[[Category: Zhang X]]
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[[Category: Helix-hairpin-helix]]
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[[Category: Hydrolase-dna complex]]
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[[Category: N-glycosidic bond]]
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[[Category: Stable intermediate]]
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Current revision

mouse MBD4 glycosylase domain in complex with DNA containing a ribose sugar

PDB ID 4ew4

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