3ksb: Difference between revisions
New page: '''Unreleased structure''' The entry 3ksb is ON HOLD Authors: Laponogov, I., Pan, X.-S., Veselkov, D.A., McAuley, K.E., Fisher, L.M., Sanderson, M.R. Description: Detailed structural i... |
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==Detailed structural insight into the DNA cleavage complex of type IIA topoisomerases (re-sealed form)== | |||
<StructureSection load='3ksb' size='340' side='right'caption='[[3ksb]], [[Resolution|resolution]] 3.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3ksb]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KSB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KSB FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.5Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ksb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ksb OCA], [https://pdbe.org/3ksb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ksb RCSB], [https://www.ebi.ac.uk/pdbsum/3ksb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ksb ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PARC_STRPN PARC_STRPN] Topoisomerase IV is essential for chromosome segregation. It relaxes supercoiled DNA. Performs the decatenation events required during the replication of a circular DNA molecule.<ref>PMID:17375187</ref> <ref>PMID:20596531</ref> | |||
== 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/ks/3ksb_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=3ksb ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Type II DNA topoisomerases are ubiquitous enzymes with essential functions in DNA replication, recombination and transcription. They change DNA topology by forming a transient covalent cleavage complex with a gate-DNA duplex that allows transport of a second duplex though the gate. Despite its biological importance and targeting by anticancer and antibacterial drugs, cleavage complex formation and reversal is not understood for any type II enzyme. To address the mechanism, we have used X-ray crystallography to study sequential states in the formation and reversal of a DNA cleavage complex by topoisomerase IV from Streptococcus pneumoniae, the bacterial type II enzyme involved in chromosome segregation. A high resolution structure of the complex captured by a novel antibacterial dione reveals two drug molecules intercalated at a cleaved B-form DNA gate and anchored by drug-specific protein contacts. Dione release generated drug-free cleaved and resealed DNA complexes in which the DNA gate instead adopts an unusual A/B-form helical conformation with a Mg(2+) ion repositioned to coordinate each scissile phosphodiester group and promote reversible cleavage by active-site tyrosines. These structures, the first for putative reaction intermediates of a type II topoisomerase, suggest how a type II enzyme reseals DNA during its normal reaction cycle and illuminate aspects of drug arrest important for the development of new topoisomerase-targeting therapeutics. | |||
Structural basis of gate-DNA breakage and resealing by type II topoisomerases.,Laponogov I, Pan XS, Veselkov DA, McAuley KE, Fisher LM, Sanderson MR PLoS One. 2010 Jun 28;5(6):e11338. PMID:20596531<ref>PMID:20596531</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3ksb" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Topoisomerase 3D structures|Topoisomerase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Streptococcus pneumoniae]] | |||
[[Category: Fisher LM]] | |||
[[Category: Laponogov I]] | |||
[[Category: McAuley KE]] | |||
[[Category: Pan X-S]] | |||
[[Category: Sanderson MR]] | |||
[[Category: Veselkov DA]] | |||
Latest revision as of 19:17, 1 November 2023
Detailed structural insight into the DNA cleavage complex of type IIA topoisomerases (re-sealed form)Detailed structural insight into the DNA cleavage complex of type IIA topoisomerases (re-sealed form)
Structural highlights
FunctionPARC_STRPN Topoisomerase IV is essential for chromosome segregation. It relaxes supercoiled DNA. Performs the decatenation events required during the replication of a circular DNA molecule.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedType II DNA topoisomerases are ubiquitous enzymes with essential functions in DNA replication, recombination and transcription. They change DNA topology by forming a transient covalent cleavage complex with a gate-DNA duplex that allows transport of a second duplex though the gate. Despite its biological importance and targeting by anticancer and antibacterial drugs, cleavage complex formation and reversal is not understood for any type II enzyme. To address the mechanism, we have used X-ray crystallography to study sequential states in the formation and reversal of a DNA cleavage complex by topoisomerase IV from Streptococcus pneumoniae, the bacterial type II enzyme involved in chromosome segregation. A high resolution structure of the complex captured by a novel antibacterial dione reveals two drug molecules intercalated at a cleaved B-form DNA gate and anchored by drug-specific protein contacts. Dione release generated drug-free cleaved and resealed DNA complexes in which the DNA gate instead adopts an unusual A/B-form helical conformation with a Mg(2+) ion repositioned to coordinate each scissile phosphodiester group and promote reversible cleavage by active-site tyrosines. These structures, the first for putative reaction intermediates of a type II topoisomerase, suggest how a type II enzyme reseals DNA during its normal reaction cycle and illuminate aspects of drug arrest important for the development of new topoisomerase-targeting therapeutics. Structural basis of gate-DNA breakage and resealing by type II topoisomerases.,Laponogov I, Pan XS, Veselkov DA, McAuley KE, Fisher LM, Sanderson MR PLoS One. 2010 Jun 28;5(6):e11338. PMID:20596531[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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