|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal structure of TDP2 from C. elegans== | | ==Crystal structure of TDP2 from C. elegans== |
| - | <StructureSection load='4gew' size='340' side='right' caption='[[4gew]], [[Resolution|resolution]] 2.35Å' scene=''> | + | <StructureSection load='4gew' size='340' side='right'caption='[[4gew]], [[Resolution|resolution]] 2.35Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4gew]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Caeel Caeel]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GEW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GEW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4gew]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GEW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GEW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.35Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4fpv|4fpv]], [[4f1h|4f1h]], [[4f1i|4f1i]], [[4fva|4fva]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Y63D3A.4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6239 CAEEL])</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=4gew FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gew OCA], [https://pdbe.org/4gew PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gew RCSB], [https://www.ebi.ac.uk/pdbsum/4gew PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gew 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=4gew FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gew OCA], [http://pdbe.org/4gew PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gew RCSB], [http://www.ebi.ac.uk/pdbsum/4gew PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gew ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TYDP2_CAEEL TYDP2_CAEEL]] DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 5'-phosphodiester bond, giving rise to DNA with a free 5' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase 2 (TOP2) active site tyrosine residue. Hydrolyzes 5'-phosphoglycolates on protruding 5' ends on DNA double-strand breaks (DSBs) due to DNA damage by radiation and free radicals (By similarity). | + | [https://www.uniprot.org/uniprot/TYDP2_CAEEL TYDP2_CAEEL] DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 5'-phosphodiester bond, giving rise to DNA with a free 5' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase 2 (TOP2) active site tyrosine residue. Hydrolyzes 5'-phosphoglycolates on protruding 5' ends on DNA double-strand breaks (DSBs) due to DNA damage by radiation and free radicals (By similarity). |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The DNA-repair enzyme Tdp2 resolves 5'-phosphotyrosyl DNA adducts and mediates resistance to anticancer drugs that target covalent topoisomerase-DNA complexes. Tdp2 also participates in key signaling pathways during development and tumorigenesis and cleaves a protein-RNA linkage during picornavirus replication. The crystal structure of zebrafish Tdp2 bound to DNA reveals a deep, narrow basic groove that selectively accommodates the 5' end of single-stranded DNA in a stretched conformation. The crystal structure of the full-length Caenorhabditis elegans Tdp2 shows that this groove can also accommodate an acidic peptide stretch in vitro, with glutamate and aspartate side chains occupying the DNA backbone phosphate-binding sites. This extensive molecular mimicry suggests a potential mechanism for autoregulation and interaction of Tdp2 with phosphorylated proteins in signaling. Our study provides a framework to interrogate functions of Tdp2 and develop inhibitors for chemotherapeutic and antiviral applications.
| + | |
| - | | + | |
| - | Structural basis for recognition of 5'-phosphotyrosine adducts by Tdp2.,Shi K, Kurahashi K, Gao R, Tsutakawa SE, Tainer JA, Pommier Y, Aihara H Nat Struct Mol Biol. 2012 Dec;19(12):1372-7. doi: 10.1038/nsmb.2423. Epub 2012, Oct 28. PMID:23104058<ref>PMID:23104058</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 4gew" style="background-color:#fffaf0;"></div>
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Phosphodiesterase|Phosphodiesterase]] | + | *[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]] |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Caeel]] | + | [[Category: Caenorhabditis elegans]] |
| - | [[Category: Aihara, H]] | + | [[Category: Large Structures]] |
| - | [[Category: Kurahashi, K]] | + | [[Category: Aihara H]] |
| - | [[Category: Shi, K]] | + | [[Category: Kurahashi K]] |
| - | [[Category: 5'-phosphotyrosyl-dna diesterase]] | + | [[Category: Shi K]] |
| - | [[Category: Hydrolase]]
| + | |
