1a36

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(New page: 200px<br /> <applet load="1a36" size="450" color="white" frame="true" align="right" spinBox="true" caption="1a36, resolution 2.800&Aring;" /> '''TOPOISOMERASE I/DN...)
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[[Image:1a36.gif|left|200px]]<br />
 
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<applet load="1a36" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1a36, resolution 2.800&Aring;" />
 
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'''TOPOISOMERASE I/DNA COMPLEX'''<br />
 
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==Overview==
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==TOPOISOMERASE I/DNA COMPLEX==
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The three-dimensional structure of a 70-kilodalton amino terminally, truncated form of human topoisomerase I in complex with a 22-base pair, duplex oligonucleotide, determined to a resolution of 2.8 angstroms, reveals all of the structural elements of the enzyme that contact DNA. The, linker region that connects the central core of the enzyme to the, carboxyl-terminal domain assumes a coiled-coil configuration and protrudes, away from the remainder of the enzyme. The positively charged DNA-proximal, surface of the linker makes only a few contacts with the DNA downstream of, the cleavage site. In combination with the crystal structures of the, reconstituted human topoisomerase I before and after DNA cleavage, this, information suggests which amino acid residues are involved in catalyzing, phosphodiester bond breakage and religation. The structures also lead to, the proposal that the topoisomerization step occurs by a mechanism termed, "controlled rotation."
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<StructureSection load='1a36' size='340' side='right'caption='[[1a36]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1a36]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The January 2006 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Topoisomerases'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2006_1 10.2210/rcsb_pdb/mom_2006_1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A36 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1A36 FirstGlance]. <br>
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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]] 2.8&#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=1a36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a36 OCA], [https://pdbe.org/1a36 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1a36 RCSB], [https://www.ebi.ac.uk/pdbsum/1a36 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1a36 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/a3/1a36_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=1a36 ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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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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*[[Topoisomerase 3D structures|Topoisomerase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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1A36 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The following page contains interesting information on the relation of 1A36 with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb73_1.html Topoisomerases]]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1A36 OCA].
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__TOC__
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</StructureSection>
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==Reference==
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A model for the mechanism of human topoisomerase I., Stewart L, Redinbo MR, Qiu X, Hol WG, Champoux JJ, Science. 1998 Mar 6;279(5356):1534-41. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9488652 9488652]
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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: RCSB PDB Molecule of the Month]]
[[Category: Topoisomerases]]
[[Category: Topoisomerases]]
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[[Category: Champoux, J.J.]]
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[[Category: Champoux JJ]]
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[[Category: Hol, W.G.J.]]
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[[Category: Hol WGJ]]
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[[Category: Qiu, X.]]
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[[Category: Qiu X]]
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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: complex (isomerase/dna)]]
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[[Category: dna]]
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[[Category: topoisomerase i]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 15:54:56 2007''
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Current revision

TOPOISOMERASE I/DNA COMPLEX

PDB ID 1a36

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