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| | <StructureSection load='5hf7' size='340' side='right'caption='[[5hf7]], [[Resolution|resolution]] 1.54Å' scene=''> | | <StructureSection load='5hf7' size='340' side='right'caption='[[5hf7]], [[Resolution|resolution]] 1.54Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5hf7]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HF7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HF7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5hf7]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Unidentified Unidentified]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HF7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HF7 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UF2:1-(2-DEOXY-2-FLUORO-5-O-PHOSPHONO-BETA-D-ARABINOFURANOSYL)PYRIMIDINE-2,4(1H,3H)-DIONE'>UF2</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.54Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TDG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UF2:1-(2-DEOXY-2-FLUORO-5-O-PHOSPHONO-BETA-D-ARABINOFURANOSYL)PYRIMIDINE-2,4(1H,3H)-DIONE'>UF2</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=5hf7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hf7 OCA], [https://pdbe.org/5hf7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hf7 RCSB], [https://www.ebi.ac.uk/pdbsum/5hf7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hf7 ProSAT]</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=5hf7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hf7 OCA], [http://pdbe.org/5hf7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hf7 RCSB], [http://www.ebi.ac.uk/pdbsum/5hf7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hf7 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == 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. | + | [https://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;">
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| - | == Publication Abstract from PubMed ==
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| - | Thymine DNA Glycosylase (TDG) is a base excision repair enzyme functioning in DNA repair and epigenetic regulation. TDG removes thymine from mutagenic G.T mispairs arising from deamination of 5-methylcytosine (mC), and it processes other deamination-derived lesions including uracil (U). Essential for DNA demethylation, TDG excises 5-formylcytosine and 5-carboxylcytosine, derivatives of mC generated by Tet (ten-eleven translocation) enzymes. Here, we report structural and functional studies of TDG82-308, a new construct containing 29 more N-terminal residues than TDG111-308, the construct used for previous structures of DNA-bound TDG. Crystal structures and NMR experiments demonstrate that most of these N-terminal residues are disordered, for substrate- or product-bound TDG82-308 Nevertheless, G.T substrate affinity and glycosylase activity of TDG82-308 greatly exceeds that of TDG111-308 and is equivalent to full-length TDG. We report the first high-resolution structures of TDG in an enzyme-substrate complex, for G.U bound to TDG82-308 (1.54 A) and TDG111-308 (1.71 A), revealing new enzyme-substrate contacts, direct and water-mediated. We also report a structure of the TDG82-308 product complex (1.70 A). TDG82-308 forms unique enzyme-DNA interactions, supporting its value for structure-function studies. The results advance understanding of how TDG recognizes and removes modified bases from DNA, particularly those resulting from deamination.
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| - | Structural basis of damage recognition by thymine DNA glycosylase: Key roles for N-terminal residues.,Coey CT, Malik SS, Pidugu LS, Varney KM, Pozharski E, Drohat AC Nucleic Acids Res. 2016 Aug 31. pii: gkw768. PMID:27580719<ref>PMID:27580719</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 5hf7" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
| | *[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]] | | *[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]] |
| - | == References == | |
| - | <references/> | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Thymine-DNA glycosylase]] | + | [[Category: Unidentified]] |
| - | [[Category: Drohat, A C]] | + | [[Category: Drohat AC]] |
| - | [[Category: Malik, S S]] | + | [[Category: Malik SS]] |
| - | [[Category: Pozharski, E]] | + | [[Category: Pozharski E]] |
| - | [[Category: Hydrolase-dna complex]]
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| - | [[Category: Protein-dna complex]]
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