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==Crystal structure of human Tyrosyl-DNA Phosphodiesterase complexed with vanadate, octopamine and trinucleotide GTT==
==Crystal structure of human Tyrosyl-DNA Phosphodiesterase complexed with vanadate, octopamine and trinucleotide GTT==
<StructureSection load='1rh0' size='340' side='right' caption='[[1rh0]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
<StructureSection load='1rh0' size='340' side='right'caption='[[1rh0]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1rh0]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RH0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1RH0 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1rh0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RH0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RH0 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=OTS:4-(2S-AMINO-1-HYDROXYETHYL)PHENOL'>OTS</scene>, <scene name='pdbligand=SPM:SPERMINE'>SPM</scene>, <scene name='pdbligand=VO4:VANADATE+ION'>VO4</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]] 2.3&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1nop|1nop]], [[1jy1|1jy1]], [[1rff|1rff]], [[1rfi|1rfi]], [[1rg1|1rg1]], [[1rg2|1rg2]], [[1rgt|1rgt]], [[1rgu|1rgu]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OTS:4-(2S-AMINO-1-HYDROXYETHYL)PHENOL'>OTS</scene>, <scene name='pdbligand=SPM:SPERMINE'>SPM</scene>, <scene name='pdbligand=VO4:VANADATE+ION'>VO4</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TDP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=1rh0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rh0 OCA], [https://pdbe.org/1rh0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rh0 RCSB], [https://www.ebi.ac.uk/pdbsum/1rh0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rh0 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=1rh0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rh0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1rh0 RCSB], [http://www.ebi.ac.uk/pdbsum/1rh0 PDBsum]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/TYDP1_HUMAN TYDP1_HUMAN]] Defects in TDP1 are the cause of spinocerebellar ataxia autosomal recessive with axonal neuropathy (SCAN1) [MIM:[http://omim.org/entry/607250 607250]]. SCAN1 is an autosomal recessive cerebellar ataxia (ARCA) associated with peripheral axonal motor and sensory neuropathy, distal muscular atrophy, pes cavus and steppage gait as seen in Charcot-Marie-Tooth neuropathy. All affected individuals have normal intelligence.<ref>PMID:16141202</ref> <ref>PMID:15647511</ref> <ref>PMID:12244316</ref> <ref>PMID:17948061</ref> <ref>PMID:15920477</ref>
[https://www.uniprot.org/uniprot/TYDP1_HUMAN TYDP1_HUMAN] Defects in TDP1 are the cause of spinocerebellar ataxia autosomal recessive with axonal neuropathy (SCAN1) [MIM:[https://omim.org/entry/607250 607250]. SCAN1 is an autosomal recessive cerebellar ataxia (ARCA) associated with peripheral axonal motor and sensory neuropathy, distal muscular atrophy, pes cavus and steppage gait as seen in Charcot-Marie-Tooth neuropathy. All affected individuals have normal intelligence.<ref>PMID:16141202</ref> <ref>PMID:15647511</ref> <ref>PMID:12244316</ref> <ref>PMID:17948061</ref> <ref>PMID:15920477</ref>  
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/TYDP1_HUMAN TYDP1_HUMAN]] DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 3'-phosphodiester bond, giving rise to DNA with a free 3' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase I active site tyrosine residue. Hydrolyzes 3'-phosphoglycolates on protruding 3' ends on DNA double-strand breaks due to DNA damage by radiation and free radicals. Acts on blunt-ended double-strand DNA breaks and on single-stranded DNA. Has low 3'exonuclease activity and can remove a single nucleoside from the 3'end of DNA and RNA molecules with 3'hydroxyl groups. Has no exonuclease activity towards DNA or RNA with a 3'phosphate.<ref>PMID:12023295</ref> <ref>PMID:15111055</ref> <ref>PMID:15811850</ref> <ref>PMID:16141202</ref> <ref>PMID:22822062</ref>
[https://www.uniprot.org/uniprot/TYDP1_HUMAN TYDP1_HUMAN] DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 3'-phosphodiester bond, giving rise to DNA with a free 3' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase I active site tyrosine residue. Hydrolyzes 3'-phosphoglycolates on protruding 3' ends on DNA double-strand breaks due to DNA damage by radiation and free radicals. Acts on blunt-ended double-strand DNA breaks and on single-stranded DNA. Has low 3'exonuclease activity and can remove a single nucleoside from the 3'end of DNA and RNA molecules with 3'hydroxyl groups. Has no exonuclease activity towards DNA or RNA with a 3'phosphate.<ref>PMID:12023295</ref> <ref>PMID:15111055</ref> <ref>PMID:15811850</ref> <ref>PMID:16141202</ref> <ref>PMID:22822062</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rh/1rh0_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rh/1rh0_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1rh0 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
<div class="pdbe-citations 1rh0" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Phosphodiesterase|Phosphodiesterase]]
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Champoux, J J]]
[[Category: Large Structures]]
[[Category: Davies, D R]]
[[Category: Champoux JJ]]
[[Category: Hol, W G]]
[[Category: Davies DR]]
[[Category: Interthal, H]]
[[Category: Hol WG]]
[[Category: Hydrolase-dna complex]]
[[Category: Interthal H]]
[[Category: Protein-dna complex]]
[[Category: Transition state mimic]]
[[Category: Vanadate complex]]

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