1mu7: Difference between revisions

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-[[Image:1mu7.jpg|left|200px]]
-<!--
+==Crystal Structure of a Human Tyrosyl-DNA Phosphodiesterase (Tdp1)-Tungstate Complex==
-The line below this paragraph, containing "STRUCTURE_1mu7", creates the "Structure Box" on the page.
+<StructureSection load='1mu7' size='340' side='right'caption='[[1mu7]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1mu7]] 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=1MU7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MU7 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</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&#8491;</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=WO4:TUNGSTATE(VI)ION'>WO4</scene></td></tr>
-{{STRUCTURE_1mu7|  PDB=1mu7  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1mu7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mu7 OCA], [https://pdbe.org/1mu7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mu7 RCSB], [https://www.ebi.ac.uk/pdbsum/1mu7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mu7 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[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 ==
+[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 ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mu/1mu7_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </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/main_output.php?pdb_ID=1mu7 ConSurf].
+<div style="clear:both"></div>
-'''Crystal Structure of a Human Tyrosyl-DNA Phosphodiesterase (Tdp1)-Tungstate Complex'''
+==See Also==
+*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
+== References ==
-==Overview==
+<references/>
-Tyrosyl-DNA phosphodiesterase (Tdp1) is a DNA repair enzyme that catalyzes the hydrolysis of a phosphodiester bond between a tyrosine residue and a DNA 3'-phosphate. The only known example of such a linkage in eukaryotic cells occurs normally as a transient link between a type IB topoisomerase and DNA. Thus human Tdp1 is thought to be responsible for repairing lesions that occur when topoisomerase I becomes stalled on the DNA in the cell. Tdp1 has also been shown to remove glycolate from single-stranded DNA containing a 3'-phosphoglycolate, suggesting a role for Tdp1 in repair of free-radical mediated DNA double-strand breaks. We report the three-dimensional structures of human Tdp1 bound to the phosphate transition state analogs vanadate and tungstate. Each structure shows the inhibitor covalently bound to His263, confirming that this residue is the nucleophile in the first step of the catalytic reaction. Vanadate in the Tdp1-vanadate structure has a trigonal bipyramidal geometry that mimics the transition state for hydrolysis of a phosphodiester bond, while Tdp1-tungstate displays unusual octahedral coordination. The presence of low-occupancy tungstate molecules along the narrow groove of the substrate binding cleft is suggestive evidence that this groove binds ssDNA. In both cases, glycerol from the cryoprotectant solution became liganded to the vanadate or tungstate inhibitor molecules in a bidentate 1,2-diol fashion. These structural models allow predictions to be made regarding the specific binding mode of the substrate and the mechanism of catalysis.
+__TOC__
+</StructureSection>
-==About this Structure==
-MU7 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=1MU7 OCA].
-==Reference==
-Insights into substrate binding and catalytic mechanism of human tyrosyl-DNA phosphodiesterase (Tdp1) from vanadate and tungstate-inhibited structures., Davies DR, Interthal H, Champoux JJ, Hol WG, J Mol Biol. 2002 Dec 13;324(5):917-32. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12470949 12470949]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Champoux, J J.]]
+[[Category: Champoux JJ]]
-[[Category: Davies, D R.]]
+[[Category: Davies DR]]
-[[Category: Hol, W G.J.]]
+[[Category: Hol WGJ]]
-[[Category: Interthal, H.]]
+[[Category: Interthal H]]
-[[Category: Pld superfamily]]
-[[Category: Protein-tungstate complex]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 01:43:06 2008''