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1lpq

From Proteopedia

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[[Image:1lpq.gif|left|200px]]
 
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{{Structure
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==Human DNA Topoisomerase I (70 Kda) In Non-Covalent Complex With A 22 Base Pair DNA Duplex Containing an 8-oxoG Lesion==
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|PDB= 1lpq |SIZE=350|CAPTION= <scene name='initialview01'>1lpq</scene>, resolution 3.14&Aring;
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<StructureSection load='1lpq' size='340' side='right'caption='[[1lpq]], [[Resolution|resolution]] 3.14&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND=
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<table><tr><td colspan='2'>[[1lpq]] is a 3 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=1LPQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LPQ FirstGlance]. <br>
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|ACTIVITY= [http://en.wikipedia.org/wiki/DNA_topoisomerase DNA topoisomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.99.1.2 5.99.1.2]
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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]] 3.14&#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=8OG:8-OXO-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>8OG</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=1lpq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lpq OCA], [https://pdbe.org/1lpq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lpq RCSB], [https://www.ebi.ac.uk/pdbsum/1lpq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lpq ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/TOP1_HUMAN TOP1_HUMAN] Note=A chromosomal aberration involving TOP1 is found in a form of therapy-related myelodysplastic syndrome. Translocation t(11;20)(p15;q11) with NUP98.
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== Function ==
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[https://www.uniprot.org/uniprot/TOP1_HUMAN TOP1_HUMAN] Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.<ref>PMID:2833744</ref> <ref>PMID:19168442</ref> <ref>PMID:14594810</ref> <ref>PMID:16033260</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/lp/1lpq_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=1lpq ConSurf].
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<div style="clear:both"></div>
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'''Human DNA Topoisomerase I (70 Kda) In Non-Covalent Complex With A 22 Base Pair DNA Duplex Containing an 8-oxoG Lesion'''
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==See Also==
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*[[Topoisomerase 3D structures|Topoisomerase 3D structures]]
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== References ==
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==Overview==
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<references/>
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7,8-Dihydro-8-oxoguanine (8-oxoG) is the most common form of oxidative DNA damage in human cells. Biochemical studies have shown that 8-oxoG decreases the DNA cleavage activity of human topoisomerase I, an enzyme vital to DNA metabolism and stability. We present the 3.1-A crystal structure of human topoisomerase I in noncovalent complex with a DNA oligonucleotide containing 8-oxoG at the +1 position in the scissile strand. We find that 8-oxoG reorganizes the active site of human topoisomerase I into an inactive conformation relative to the structures of topoisomerase I-DNA complexes elucidated previously. The catalytic Tyr-723-Phe rotates away from the DNA cleavage site and packs into the body of the molecule. A second active-site residue, Arg-590, becomes disordered and is not observed in the structure. The docked, inactive conformation of Tyr-723-Phe is reminiscent of the related tyrosine recombinase family of integrases and recombinases, suggesting a common regulatory mechanism. We propose that human topoisomerase I binds to DNA first in an inactive conformation and then rearranges its active site for catalysis. 8-OxoG appears to impact topoisomerase I by stabilizing the inactive, DNA-bound state.
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__TOC__
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</StructureSection>
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==Disease==
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Known disease associated with this structure: DNA topoisomerase I, camptothecin-resistant OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=126420 126420]]
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==About this Structure==
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1LPQ 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=1LPQ OCA].
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==Reference==
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8-Oxoguanine rearranges the active site of human topoisomerase I., Lesher DT, Pommier Y, Stewart L, Redinbo MR, Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12102-7. Epub 2002 Sep 3. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12209008 12209008]
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[[Category: DNA topoisomerase]]
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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: Lesher, D T.]]
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[[Category: Lesher DT]]
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[[Category: Pommier, Y.]]
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[[Category: Pommier Y]]
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[[Category: Redinbo, M R.]]
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[[Category: Redinbo MR]]
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[[Category: Stewart, L.]]
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[[Category: Stewart L]]
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[[Category: dna damage]]
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[[Category: induced conformational change]]
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[[Category: protein-dna complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:33:41 2008''
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Current revision

Human DNA Topoisomerase I (70 Kda) In Non-Covalent Complex With A 22 Base Pair DNA Duplex Containing an 8-oxoG Lesion

PDB ID 1lpq

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