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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]] 1.73&Aring;' scene=''>
<StructureSection load='4fpv' size='340' side='right'caption='[[4fpv]], [[Resolution|resolution]] 1.73&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4fpv]] is a 3 chain structure with sequence from [http://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 [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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.73&#8491;</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='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='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 Danio rerio])</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='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://www.rcsb.org/pdb/explore.do?structureId=4fpv RCSB], [http://www.ebi.ac.uk/pdbsum/4fpv PDBsum]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[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>  
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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>


==See Also==
==See Also==
*[[Phosphodiesterase|Phosphodiesterase]]
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Danio 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]]
Retrieved from "https://proteopedia.org/4fpv"