1pvg

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(New page: 200px<br /><applet load="1pvg" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pvg, resolution 1.80&Aring;" /> '''Crystal Structure of...)
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[[Image:1pvg.gif|left|200px]]<br /><applet load="1pvg" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1pvg, resolution 1.80&Aring;" />
 
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'''Crystal Structure of the ATPase region of Saccharomyces Cerevisiae topoisomerase II'''<br />
 
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==Overview==
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==Crystal Structure of the ATPase region of Saccharomyces Cerevisiae topoisomerase II==
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Type IIA topoisomerases both manage the topological state of chromosomal, DNA and are the targets of a variety of clinical agents., Bisdioxopiperazines are anticancer agents that associate with ATP-bound, eukaryotic topoisomerase II (topo II) and convert the enzyme into an, inactive, salt-stable clamp around DNA. To better understand both topo II, and bisdioxopiperazine function, we determined the structures of the, adenosine 5'-[beta,gamma-imino]-triphosphate-bound yeast topo II ATPase, region (ScT2-ATPase) alone and complexed with the bisdioxopiperazine, ICRF-187. The drug-free form of the protein is similar in overall fold to, the equivalent region of bacterial gyrase but unexpectedly displays, significant conformational differences. The ternary drug-bound complex, reveals that ICRF-187 acts by an unusual mechanism of inhibition in which, the drug does not compete for the ATP-binding pocket, but bridges and, stabilizes a transient dimer interface between two ATPase protomers. Our, data explain why bisdioxopiperazines target ATP-bound topo II, provide a, structural rationale for the effects of certain drug-resistance mutations, and point to regions of bisdioxopiperazines that might be modified to, improve or alter drug specificity.
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<StructureSection load='1pvg' size='340' side='right'caption='[[1pvg]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1pvg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PVG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PVG 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]] 1.8&#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=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=1pvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pvg OCA], [https://pdbe.org/1pvg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pvg RCSB], [https://www.ebi.ac.uk/pdbsum/1pvg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pvg ProSAT]</span></td></tr>
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</table>
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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/pv/1pvg_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1pvg ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Type IIA topoisomerases both manage the topological state of chromosomal DNA and are the targets of a variety of clinical agents. Bisdioxopiperazines are anticancer agents that associate with ATP-bound eukaryotic topoisomerase II (topo II) and convert the enzyme into an inactive, salt-stable clamp around DNA. To better understand both topo II and bisdioxopiperazine function, we determined the structures of the adenosine 5'-[beta,gamma-imino]-triphosphate-bound yeast topo II ATPase region (ScT2-ATPase) alone and complexed with the bisdioxopiperazine ICRF-187. The drug-free form of the protein is similar in overall fold to the equivalent region of bacterial gyrase but unexpectedly displays significant conformational differences. The ternary drug-bound complex reveals that ICRF-187 acts by an unusual mechanism of inhibition in which the drug does not compete for the ATP-binding pocket, but bridges and stabilizes a transient dimer interface between two ATPase protomers. Our data explain why bisdioxopiperazines target ATP-bound topo II, provide a structural rationale for the effects of certain drug-resistance mutations, and point to regions of bisdioxopiperazines that might be modified to improve or alter drug specificity.
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==About this Structure==
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Structure of the topoisomerase II ATPase region and its mechanism of inhibition by the chemotherapeutic agent ICRF-187.,Classen S, Olland S, Berger JM Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10629-34. Epub 2003 Sep 8. PMID:12963818<ref>PMID:12963818</ref>
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1PVG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with MG and ANP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/DNA_topoisomerase_(ATP-hydrolyzing) DNA topoisomerase (ATP-hydrolyzing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.99.1.3 5.99.1.3] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1PVG OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Structure of the topoisomerase II ATPase region and its mechanism of inhibition by the chemotherapeutic agent ICRF-187., Classen S, Olland S, Berger JM, Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10629-34. Epub 2003 Sep 8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12963818 12963818]
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</div>
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[[Category: DNA topoisomerase (ATP-hydrolyzing)]]
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<div class="pdbe-citations 1pvg" style="background-color:#fffaf0;"></div>
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[[Category: Saccharomyces cerevisiae]]
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[[Category: Single protein]]
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[[Category: Berger, J.M.]]
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[[Category: Classen, S.]]
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[[Category: Olland, S.]]
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[[Category: ANP]]
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[[Category: MG]]
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[[Category: ghkl atpase domain]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 00:09:26 2007''
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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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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
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[[Category: Saccharomyces cerevisiae]]
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[[Category: Berger JM]]
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[[Category: Classen S]]
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[[Category: Olland S]]

Current revision

Crystal Structure of the ATPase region of Saccharomyces Cerevisiae topoisomerase II

PDB ID 1pvg

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