1qzq

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[[Image:1qzq.gif|left|200px]]
 
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==human Tyrosyl DNA phosphodiesterase==
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The line below this paragraph, containing "STRUCTURE_1qzq", creates the "Structure Box" on the page.
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<StructureSection load='1qzq' size='340' side='right'caption='[[1qzq]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1qzq]] is a 2 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=1QZQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QZQ FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.4&#8491;</td></tr>
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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=1qzq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qzq OCA], [https://pdbe.org/1qzq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qzq RCSB], [https://www.ebi.ac.uk/pdbsum/1qzq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qzq ProSAT]</span></td></tr>
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{{STRUCTURE_1qzq| PDB=1qzq | SCENE= }}
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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/qz/1qzq_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=1qzq ConSurf].
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<div style="clear:both"></div>
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'''human Tyrosyl DNA phosphodiesterase'''
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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 I (Tdp1) is involved in the repair of DNA lesions created by topoisomerase I in vivo. Tdp1 is a member of the phospholipase D (PLD) superfamily of enzymes and hydrolyzes 3'-phosphotyrosyl bonds to generate 3'-phosphate DNA and free tyrosine in vitro. Here, we use synthetic 3'-(4-nitro)phenyl, 3'-(4-methyl)phenyl, and 3'-tyrosine phosphate oligonucleotides to study human Tdp1. Kinetic analysis of human Tdp1 (hTdp1) shows that the enzyme has nanomolar affinity for all three substrates and the overall in vitro reaction is diffusion-limited. Analysis of active-site mutants using these modified substrates demonstrates that hTdp1 uses an acid/base catalytic mechanism. The results show that histidine 493 serves as the general acid during the initial transesterification, in agreement with hypotheses based on previous crystal structure models. The results also argue that lysine 495 and asparagine 516 participate in the general acid reaction, and the analysis of crystal structures suggests that these residues may function in a proton relay. Together with previous crystal structure data, the new functional data provide a mechanistic understanding of the conserved histidine, lysine and asparagine residues found among all PLD family members.
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__TOC__
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</StructureSection>
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==About this Structure==
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1QZQ 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=1QZQ OCA].
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==Reference==
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Analysis of human tyrosyl-DNA phosphodiesterase I catalytic residues., Raymond AC, Rideout MC, Staker B, Hjerrild K, Burgin AB Jr, J Mol Biol. 2004 May 14;338(5):895-906. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15111055 15111055]
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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: Hjerrild, K.]]
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[[Category: Burgin Jr AB]]
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[[Category: Jr., A B.Burgin.]]
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[[Category: Hjerrild K]]
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[[Category: Raymond, A C.]]
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[[Category: Raymond AC]]
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[[Category: Rideout, M C.]]
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[[Category: Rideout MC]]
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[[Category: Staker, B.]]
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[[Category: Staker B]]
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[[Category: Dna repair]]
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[[Category: Replication]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 06:54:00 2008''
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Current revision

human Tyrosyl DNA phosphodiesterase

PDB ID 1qzq

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