4ea4: Difference between revisions

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-[[Image:4ea4.png|left|200px]]
+==Structure of the glycosylase domain of MBD4 bound to 5hmU-containing DNA==
+<StructureSection load='4ea4' size='340' side='right' caption='[[4ea4]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4ea4]] is a 3 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=4EA4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EA4 FirstGlance]. <br>
+</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=5HU:5-HYDROXYMETHYLURIDINE-2-DEOXY-5-MONOPHOSPHATE'>5HU</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4e9e|4e9e]], [[4e9f|4e9f]], [[4e9g|4e9g]], [[4e9h|4e9h]], [[4eab|4eab]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MBD4, MED1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4ea4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ea4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ea4 RCSB], [http://www.ebi.ac.uk/pdbsum/4ea4 PDBsum]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Active DNA demethylation in mammals occurs via hydroxylation of 5-methylcytosine to 5-hydroxymethylcytosine (5hmC) by the ten-eleven translocation family of proteins (TETs). 5hmC residues in DNA can be further oxidized by TETs to 5-carboxylcytosines and/or deaminated by the Activation Induced Deaminase/Apolipoprotein B mRNA-editing enzyme complex family proteins to 5-hydromethyluracil (5hmU). Excision and replacement of these intermediates is initiated by DNA glycosylases such as thymine-DNA glycosylase (TDG), methyl-binding domain protein 4 (MBD4) and single-strand specific monofunctional uracil-DNA glycosylase 1 in the base excision repair pathway. Here, we report detailed biochemical and structural characterization of human MBD4 which contains mismatch-specific TDG activity. Full-length as well as catalytic domain (residues 426-580) of human MBD4 (MBD4(cat)) can remove 5hmU when opposite to G with good efficiency. Here, we also report six crystal structures of human MBD4(cat): an unliganded form and five binary complexes with duplex DNA containing a T*G, 5hmU*G or AP*G (apurinic/apyrimidinic) mismatch at the target base pair. These structures reveal that MBD4(cat) uses a base flipping mechanism to specifically recognize thymine and 5hmU. The recognition mechanism of flipped-out 5hmU bases in MBD4(cat) active site supports the potential role of MBD4, together with TDG, in maintenance of genome stability and active DNA demethylation in mammals.
-{{STRUCTURE_4ea4|  PDB=4ea4  |  SCENE=  }}
+Biochemical and structural characterization of the glycosylase domain of MBD4 bound to thymine and 5-hydroxymethyuracil-containing DNA.,Morera S, Grin I, Vigouroux A, Couve S, Henriot V, Saparbaev M, Ishchenko AA Nucleic Acids Res. 2012 Jul 30. PMID:22848106<ref>PMID:22848106</ref>
-===Structure of the glycosylase domain of MBD4 bound to 5hmU-containing DNA===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+==See Also==
-==About this Structure==
+*[[Methyl CpG binding protein|Methyl CpG binding protein]]
-[[4ea4]] is a 3 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=4EA4 OCA].
+== References ==
+<references/>
-==Reference==
+__TOC__
-<ref group="xtra">PMID:022848106</ref><references group="xtra"/>
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Morera, S.]]
+[[Category: Morera, S]]
-[[Category: Vigouroux, A.]]
+[[Category: Vigouroux, A]]
 [[Category: Hhh dna glycosylase family]]
 [[Category: Hydrolase-dna complex]]