4z47: Difference between revisions

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-'''Unreleased structure'''
+==Structure of the enzyme-product complex resulting from TDG action on a GU mismatch in the presence of excess base==
+<StructureSection load='4z47' size='340' side='right' caption='[[4z47]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4z47]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z47 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Z47 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ORP:2-DEOXY-5-PHOSPHONO-RIBOSE'>ORP</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4z7z|4z7z]], [[4z7b|4z7b]], [[4xeg|4xeg]], [[4z3a|4z3a]], [[5cys|5cys]]</td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymine-DNA_glycosylase Thymine-DNA glycosylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.29 3.2.2.29] </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=4z47 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z47 OCA], [http://pdbe.org/4z47 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4z47 RCSB], [http://www.ebi.ac.uk/pdbsum/4z47 PDBsum]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/TDG_HUMAN TDG_HUMAN]] In the DNA of higher eukaryotes, hydrolytic deamination of 5-methylcytosine to thymine leads to the formation of G/T mismatches. This enzyme corrects G/T mispairs to G/C pairs. It is capable of hydrolyzing the carbon-nitrogen bond between the sugar-phosphate backbone of the DNA and a mispaired thymine. In addition to the G/T, it can remove thymine also from C/T and T/T mispairs in the order G/T >> C/T > T/T. It has no detectable activity on apyrimidinic sites and does not catalyze the removal of thymine from A/T pairs or from single-stranded DNA. It can also remove uracil and 5-bromouracil from mispairs with guanine.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Thymine DNA Glycosylase (TDG) performs essential functions in maintaining genetic integrity and epigenetic regulation. Initiating base excision repair, TDG removes thymine from mutagenic G .: T mispairs caused by 5-methylcytosine (mC) deamination and other lesions including uracil (U) and 5-hydroxymethyluracil (hmU). In DNA demethylation, TDG excises 5-formylcytosine (fC) and 5-carboxylcytosine (caC), which are generated from mC by Tet (ten-eleven translocation) enzymes. Using improved crystallization conditions, we solved high-resolution (up to 1.45 A) structures of TDG enzyme-product complexes generated from substrates including G.U, G.T, G.hmU, G.fC and G.caC. The structures reveal many new features, including key water-mediated enzyme-substrate interactions. Together with nuclear magnetic resonance experiments, the structures demonstrate that TDG releases the excised base from its tight product complex with abasic DNA, contrary to previous reports. Moreover, DNA-free TDG exhibits no significant binding to free nucleobases (U, T, hmU), indicating a Kd &gt;&gt; 10 mM. The structures reveal a solvent-filled channel to the active site, which might facilitate dissociation of the excised base and enable caC excision, which involves solvent-mediated acid catalysis. Dissociation of the excised base allows TDG to bind the beta rather than the alpha anomer of the abasic sugar, which might stabilize the enzyme-product complex.
-The entry 4z47 is ON HOLD  until Paper Publication
+Thymine DNA glycosylase exhibits negligible affinity for nucleobases that it removes from DNA.,Malik SS, Coey CT, Varney KM, Pozharski E, Drohat AC Nucleic Acids Res. 2015 Sep 10. pii: gkv890. PMID:26358812<ref>PMID:26358812</ref>
-Authors: Pozharski, E., Malik, S.S., Drohat, A.C.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description: Structure of the enzyme-product complex resulting from TDG action on a GU mismatch in the presence of excess base
+<div class="pdbe-citations 4z47" style="background-color:#fffaf0;"></div>
-[[Category: Unreleased Structures]]
+== References ==
-[[Category: Malik, S.S]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Thymine-DNA glycosylase]]
+[[Category: Drohat, A C]]
+[[Category: Malik, S S]]
 [[Category: Pozharski, E]]
-[[Category: Drohat, A.C]]
+[[Category: Dna binding protein-dna complex]]
+[[Category: Protein-dna complex]]