1nop

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[[Image:1nop.gif|left|200px]]
 
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{{Structure
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==Crystal structure of human tyrosyl-DNA phosphodiesterase (Tdp1) in complex with vanadate, DNA and a human topoisomerase I-derived peptide==
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|PDB= 1nop |SIZE=350|CAPTION= <scene name='initialview01'>1nop</scene>, resolution 2.30&Aring;
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<StructureSection load='1nop' size='340' side='right'caption='[[1nop]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=VO4:VANADATE ION'>VO4</scene>
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<table><tr><td colspan='2'>[[1nop]] is a 5 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=1NOP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NOP FirstGlance]. <br>
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|ACTIVITY=
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</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>
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|GENE=
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VO4:VANADATE+ION'>VO4</scene></td></tr>
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}}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1nop FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nop OCA], [https://pdbe.org/1nop PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nop RCSB], [https://www.ebi.ac.uk/pdbsum/1nop PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nop ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/no/1nop_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1nop ConSurf].
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<div style="clear:both"></div>
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'''Crystal structure of human tyrosyl-DNA phosphodiesterase (Tdp1) in complex with vanadate, DNA and a human topoisomerase I-derived peptide'''
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==See Also==
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*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
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== References ==
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==Overview==
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<references/>
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Tyrosyl-DNA phosphodiesterase (Tdp1) is a member of the phospholipase D superfamily and acts as a DNA repair enzyme that removes stalled topoisomerase I- DNA complexes by hydrolyzing the bond between a tyrosine side chain and a DNA 3' phosphate. Despite the complexity of the substrate of this phosphodiesterase, vanadate succeeded in linking human Tdp1, a tyrosine-containing peptide, and a single-stranded DNA oligonucleotide into a quaternary complex that mimics the transition state for the first step of the catalytic reaction. The conformation of the bound substrate mimic gives compelling evidence that the topoisomerase I-DNA complex must undergo extensive modification prior to cleavage by Tdp1. The structure also illustrates that the use of vanadate as the central moiety in high-order complexes has the potential to be a general method for capturing protein-substrate interactions for phosphoryl transfer enzymes, even when the substrates are large, complicated, and unusual.
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__TOC__
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</StructureSection>
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==About this Structure==
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1NOP is a [[Single protein]] structure of 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=1NOP OCA].
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==Reference==
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Crystal structure of a transition state mimic for Tdp1 assembled from vanadate, DNA, and a topoisomerase I-derived peptide., Davies DR, Interthal H, Champoux JJ, Hol WG, Chem Biol. 2003 Feb;10(2):139-47. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12618186 12618186]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Champoux, J J.]]
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[[Category: Champoux JJ]]
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[[Category: Davies, D R.]]
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[[Category: Davies DR]]
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[[Category: Hol, W G.J.]]
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[[Category: Hol WGJ]]
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[[Category: Interthal, H.]]
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[[Category: Interthal H]]
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[[Category: VO4]]
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[[Category: protein-dna complex]]
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[[Category: transition state mimic]]
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[[Category: vanadate complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:59:39 2008''
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Current revision

Crystal structure of human tyrosyl-DNA phosphodiesterase (Tdp1) in complex with vanadate, DNA and a human topoisomerase I-derived peptide

PDB ID 1nop

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