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[[Image:2h7g.gif|left|200px]]


{{Structure
==Structure of variola topoisomerase non-covalently bound to DNA==
|PDB= 2h7g |SIZE=350|CAPTION= <scene name='initialview01'>2h7g</scene>, resolution 1.900&Aring;
<StructureSection load='2h7g' size='340' side='right'caption='[[2h7g]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
|SITE=
== Structural highlights ==
|LIGAND= <scene name='pdbligand=DA:2&#39;-DEOXYADENOSINE-5&#39;-MONOPHOSPHATE'>DA</scene>, <scene name='pdbligand=DC:2&#39;-DEOXYCYTIDINE-5&#39;-MONOPHOSPHATE'>DC</scene>, <scene name='pdbligand=DG:2&#39;-DEOXYGUANOSINE-5&#39;-MONOPHOSPHATE'>DG</scene>, <scene name='pdbligand=DT:THYMIDINE-5&#39;-MONOPHOSPHATE'>DT</scene>
<table><tr><td colspan='2'>[[2h7g]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Variola_virus Variola virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H7G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H7G FirstGlance]. <br>
|ACTIVITY= <span class='plainlinks'>[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] </span>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
|GENE= TOP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10255 Variola virus])
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2h7g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h7g OCA], [https://pdbe.org/2h7g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h7g RCSB], [https://www.ebi.ac.uk/pdbsum/2h7g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h7g ProSAT]</span></td></tr>
|DOMAIN=
</table>
|RELATEDENTRY=[[2h7f|2H7F]]
== Function ==
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2h7g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h7g OCA], [http://www.ebi.ac.uk/pdbsum/2h7g PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2h7g RCSB]</span>
[https://www.uniprot.org/uniprot/TOP1_VAR67 TOP1_VAR67] 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 the specific target site 5'-[CT]CCTTp 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).
}}
== 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/h7/2h7g_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=2h7g ConSurf].
<div style="clear:both"></div>


'''Structure of variola topoisomerase non-covalently bound to DNA'''
==See Also==
 
*[[Topoisomerase 3D structures|Topoisomerase 3D structures]]
 
__TOC__
==Overview==
</StructureSection>
Although smallpox has been eradicated from the human population, it is presently feared as a possible agent of bioterrorism. The smallpox virus codes for its own topoisomerase enzyme that differs from its cellular counterpart by requiring a specific DNA sequence for activation of catalysis. Here we present crystal structures of the smallpox virus topoisomerase enzyme bound both covalently and noncovalently to a specific DNA sequence. These structures reveal the basis for site-specific DNA recognition, and they explain how catalysis is likely activated by formation of a specific enzyme-DNA interface. Unexpectedly, the poxvirus enzyme uses a major groove binding alpha helix that is not present in the human enzyme to recognize part of the core recognition sequence and activate the enzyme for catalysis. The topoisomerase-DNA complex structures also provide a three-dimensional framework that may facilitate the rational design of therapeutic agents to treat poxvirus infections.
[[Category: Large Structures]]
 
==About this Structure==
2H7G is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Variola_virus Variola virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H7G OCA].
 
==Reference==
Structural basis for specificity in the poxvirus topoisomerase., Perry K, Hwang Y, Bushman FD, Van Duyne GD, Mol Cell. 2006 Aug 4;23(3):343-54. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16885024 16885024]
[[Category: DNA topoisomerase]]
[[Category: Single protein]]
[[Category: Variola virus]]
[[Category: Variola virus]]
[[Category: Bushman, F D.]]
[[Category: Bushman FD]]
[[Category: Duyne, G D.Van.]]
[[Category: Hwang Y]]
[[Category: Hwang, Y.]]
[[Category: Perry K]]
[[Category: Perry, K.]]
[[Category: Van Duyne GD]]
[[Category: dna binding]]
[[Category: isomerase]]
[[Category: protein-dna complex]]
[[Category: type ib topoisomerase]]
 
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