1qzr

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[[Image:1qzr.gif|left|200px]]
[[Image:1qzr.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 1qzr |SIZE=350|CAPTION= <scene name='initialview01'>1qzr</scene>, resolution 1.90&Aring;
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The line below this paragraph, containing "STRUCTURE_1qzr", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=CDX:(S)-4,4&#39;-(1-METHYL-1,2-ETHANEDIYL)BIS-2,6-PIPERAZINEDIONE'>CDX</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[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] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE= TOP2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae])
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-->
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|DOMAIN=
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{{STRUCTURE_1qzr| PDB=1qzr | SCENE= }}
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|RELATEDENTRY=[[1pvg|1PVG]], [[1bgw|1BGW]], [[1bjt|1BJT]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1qzr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qzr OCA], [http://www.ebi.ac.uk/pdbsum/1qzr PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1qzr RCSB]</span>
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}}
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'''CRYSTAL STRUCTURE OF THE ATPASE REGION OF SACCHAROMYCES CEREVISIAE TOPOISOMERASE II BOUND TO ICRF-187 (DEXRAZOXANE)'''
'''CRYSTAL STRUCTURE OF THE ATPASE REGION OF SACCHAROMYCES CEREVISIAE TOPOISOMERASE II BOUND TO ICRF-187 (DEXRAZOXANE)'''
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==About this Structure==
==About this Structure==
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1QZR is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. This structure supersedes the now removed PDB entry 1Q1D. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QZR OCA].
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1QZR is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1q1d 1q1d]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QZR OCA].
==Reference==
==Reference==
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://www.ncbi.nlm.nih.gov/pubmed/12963818 12963818]
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://www.ncbi.nlm.nih.gov/pubmed/12963818 12963818]
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[[Category: DNA topoisomerase (ATP-hydrolyzing)]]
 
[[Category: Saccharomyces cerevisiae]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Classen, S.]]
[[Category: Classen, S.]]
[[Category: Olland, S.]]
[[Category: Olland, S.]]
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[[Category: dexrazoxane]]
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[[Category: Dexrazoxane]]
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[[Category: ghkl atpase domain]]
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[[Category: Ghkl atpase domain]]
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[[Category: icrf]]
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[[Category: Icrf]]
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[[Category: icrf-187]]
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[[Category: Icrf-187]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 06:53:59 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:21:13 2008''
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Revision as of 03:54, 3 May 2008

Image:1qzr.gif

Template:STRUCTURE 1qzr

CRYSTAL STRUCTURE OF THE ATPASE REGION OF SACCHAROMYCES CEREVISIAE TOPOISOMERASE II BOUND TO ICRF-187 (DEXRAZOXANE)


Overview

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.

About this Structure

1QZR is a Single protein structure of sequence from Saccharomyces cerevisiae. This structure supersedes the now removed PDB entry 1q1d. Full crystallographic information is available from OCA.

Reference

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 Page seeded by OCA on Sat May 3 06:53:59 2008

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