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1a31

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(New page: 200px<br /> <applet load="1a31" size="450" color="white" frame="true" align="right" spinBox="true" caption="1a31, resolution 2.1&Aring;" /> '''HUMAN RECONSTITUTED ...)
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[[Image:1a31.gif|left|200px]]<br />
 
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<applet load="1a31" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1a31, resolution 2.1&Aring;" />
 
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'''HUMAN RECONSTITUTED DNA TOPOISOMERASE I IN COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX'''<br />
 
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==Overview==
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==HUMAN RECONSTITUTED DNA TOPOISOMERASE I IN COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX==
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Topoisomerases I promote the relaxation of DNA superhelical tension by, introducing a transient single-stranded break in duplex DNA and are vital, for the processes of replication, transcription, and recombination. The, crystal structures at 2.1 and 2.5 angstrom resolution of reconstituted, human topoisomerase I comprising the core and carboxyl-terminal domains in, covalent and noncovalent complexes with 22-base pair DNA duplexes reveal, an enzyme that "clamps" around essentially B-form DNA. The core domain and, the first eight residues of the carboxyl-terminal domain of the enzyme, including the active-site nucleophile tyrosine-723, share significant, structural similarity with the bacteriophage family of DNA integrases. A, binding mode for the anticancer drug camptothecin is proposed on the basis, of chemical and biochemical information combined with these, three-dimensional structures of topoisomerase I-DNA complexes.
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<StructureSection load='1a31' size='340' side='right'caption='[[1a31]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1a31]] 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=1A31 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1A31 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]] 2.1&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5IU:5-IODO-2-DEOXYURIDINE-5-MONOPHOSPHATE'>5IU</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></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=1a31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a31 OCA], [https://pdbe.org/1a31 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1a31 RCSB], [https://www.ebi.ac.uk/pdbsum/1a31 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1a31 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/a3/1a31_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=1a31 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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1A31 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 1A31 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=1A31 OCA].
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__TOC__
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</StructureSection>
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==Reference==
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Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA., Redinbo MR, Stewart L, Kuhn P, Champoux JJ, Hol WG, Science. 1998 Mar 6;279(5356):1504-13. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9488644 9488644]
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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: Kuhn, P.]]
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[[Category: Kuhn P]]
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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]]
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[[Category: topoisomerase i]]
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[[Category: topoisomerase i/dna]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 15:54:50 2007''
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Current revision

HUMAN RECONSTITUTED DNA TOPOISOMERASE I IN COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX

PDB ID 1a31

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