|
|
| Line 3: |
Line 3: |
| | <StructureSection load='4z7b' size='340' side='right'caption='[[4z7b]], [[Resolution|resolution]] 2.02Å' scene=''> | | <StructureSection load='4z7b' size='340' side='right'caption='[[4z7b]], [[Resolution|resolution]] 2.02Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4z7b]] 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=4Z7B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Z7B FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4z7b]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=4Z7B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Z7B 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> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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">[[4z3a|4z3a]], [[4z47|4z47]], [[4z7z|4z7z]], [[4xeg|4xeg]], [[5cys|5cys]]</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=4z7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z7b OCA], [https://pdbe.org/4z7b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4z7b RCSB], [https://www.ebi.ac.uk/pdbsum/4z7b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4z7b ProSAT]</span></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='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=4z7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z7b OCA], [http://pdbe.org/4z7b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4z7b RCSB], [http://www.ebi.ac.uk/pdbsum/4z7b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4z7b 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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 28: |
Line 25: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Thymine-DNA glycosylase]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Drohat, A C]] | + | [[Category: Drohat AC]] |
| - | [[Category: Malik, S S]] | + | [[Category: Malik SS]] |
| - | [[Category: Pozharski, E]] | + | [[Category: Pozharski E]] |
| - | [[Category: Hydrolase-dna complex]]
| + | |
| - | [[Category: Protein-dna complex]]
| + | |
| Structural highlights
Function
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.
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 >> 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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Malik SS, Coey CT, Varney KM, Pozharski E, Drohat AC. Thymine DNA glycosylase exhibits negligible affinity for nucleobases that it removes from DNA. Nucleic Acids Res. 2015 Sep 10. pii: gkv890. PMID:26358812 doi:http://dx.doi.org/10.1093/nar/gkv890
|
