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| | ==Crystal structure of D. rerio TDP2 complexed with single strand DNA product== | | ==Crystal structure of D. rerio TDP2 complexed with single strand DNA product== |
| - | <StructureSection load='4fpv' size='340' side='right' caption='[[4fpv]], [[Resolution|resolution]] 1.73Å' scene=''> | + | <StructureSection load='4fpv' size='340' side='right'caption='[[4fpv]], [[Resolution|resolution]] 1.73Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4fpv]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FPV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FPV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4fpv]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FPV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FPV 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>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | + | </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>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4f1h|4f1h]], [[4f1i|4f1i]], [[4fva|4fva]], [[4gew|4gew]]</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=4fpv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fpv OCA], [https://pdbe.org/4fpv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fpv RCSB], [https://www.ebi.ac.uk/pdbsum/4fpv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fpv ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">tdp2, ttrap, ttrapl, si:ch211-81e5.5, si:dkey-218n20.5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7955 Brachidanio rerio])</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=4fpv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fpv OCA], [http://pdbe.org/4fpv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fpv RCSB], [http://www.ebi.ac.uk/pdbsum/4fpv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4fpv ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TYDP2_DANRE TYDP2_DANRE]] 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). Controls gastrulation movements and left/right (L/R) axis determination via smad3-mediated regulation of cdh1/e-cadherin. Regulates the formation of Kupffer's vesicle, a signaling center essential for establishing L/R asymmetry. Modulates smad3 activity through modulating nodal-acvr1/akt4 signaling.<ref>PMID:18039968</ref> | + | [https://www.uniprot.org/uniprot/TYDP2_DANRE TYDP2_DANRE] 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). Controls gastrulation movements and left/right (L/R) axis determination via smad3-mediated regulation of cdh1/e-cadherin. Regulates the formation of Kupffer's vesicle, a signaling center essential for establishing L/R asymmetry. Modulates smad3 activity through modulating nodal-acvr1/akt4 signaling.<ref>PMID:18039968</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4fpv" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4fpv" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Brachidanio rerio]] | + | [[Category: Danio rerio]] |
| - | [[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-dna complex]]
| + | |
| Structural highlights
Function
TYDP2_DANRE 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). Controls gastrulation movements and left/right (L/R) axis determination via smad3-mediated regulation of cdh1/e-cadherin. Regulates the formation of Kupffer's vesicle, a signaling center essential for establishing L/R asymmetry. Modulates smad3 activity through modulating nodal-acvr1/akt4 signaling.[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Esguerra CV, Nelles L, Vermeire L, Ibrahimi A, Crawford AD, Derua R, Janssens E, Waelkens E, Carmeliet P, Collen D, Huylebroeck D. Ttrap is an essential modulator of Smad3-dependent Nodal signaling during zebrafish gastrulation and left-right axis determination. Development. 2007 Dec;134(24):4381-93. PMID:18039968 doi:http://dx.doi.org/134/24/4381
- ↑ Shi K, Kurahashi K, Gao R, Tsutakawa SE, Tainer JA, Pommier Y, Aihara H. Structural basis for recognition of 5'-phosphotyrosine adducts by Tdp2. Nat Struct Mol Biol. 2012 Dec;19(12):1372-7. doi: 10.1038/nsmb.2423. Epub 2012, Oct 28. PMID:23104058 doi:http://dx.doi.org/10.1038/nsmb.2423
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