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[[Image:2vub.gif|left|200px]]<br /><applet load="2vub" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2vub, resolution 2.45&Aring;" />
'''CCDB, A TOPOISOMERASE POISON FROM E. COLI'''<br />


==Overview==
==CCDB, A TOPOISOMERASE POISON FROM E. COLI==
The crystal structure of CcdB, a protein that poisons Escherichia coli gyrase, was determined in three crystal forms. The protein consists of a five-stranded antiparallel beta-pleated sheet followed by a C-terminal alpha-helix. In one of the loops of the sheet, a second small three-stranded antiparallel beta-sheet is inserted that sticks out of the molecule as a wing. This wing contains the LysC proteolytic cleavage site that is protected by CcdA and, therefore, forms a likely CcdA recognition site. A dimer is formed by sheet extension and by extensive hydrophobic contacts involving three of the five methionine residues and the C terminus of the alpha-helix. The surface of the dimer on the side of the alpha-helix is overall negatively charged, while the opposite side as well as the wing sheet is dominated by positive charges. We propose that the CcdB dimer binds into the central hole of the 59 kDa N-terminal fragment of GyrA, after disruption of the head dimer interface of GyrA.
<StructureSection load='2vub' size='340' side='right'caption='[[2vub]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
 
== Structural highlights ==
==About this Structure==
<table><tr><td colspan='2'>[[2vub]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VUB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VUB FirstGlance]. <br>
2VUB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VUB OCA].  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.45&#8491;</td></tr>
 
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
==Reference==
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2vub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vub OCA], [https://pdbe.org/2vub PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vub RCSB], [https://www.ebi.ac.uk/pdbsum/2vub PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vub ProSAT]</span></td></tr>
Crystal structure of CcdB, a topoisomerase poison from E. coli., Loris R, Dao-Thi MH, Bahassi EM, Van Melderen L, Poortmans F, Liddington R, Couturier M, Wyns L, J Mol Biol. 1999 Jan 29;285(4):1667-77. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9917404 9917404]
</table>
== Function ==
[https://www.uniprot.org/uniprot/CCDB_ECOLI CCDB_ECOLI] Toxic component of a toxin-antitoxin (TA) module, functioning in plasmid maintainence. Responsible for the post-segregational killing (PSK) of plasmid-free cells, also referred to as a plasmid addiction system. Half-life of over 2 hours. Cell killing by CcdB is accompanied by filamentation, defects in chromosome and plasmid segregation, defects in cell division, formation of anucleate cells, decreased DNA synthesis and plasmid loss. Interferes with the activity of DNA gyrase, inducing it to form a covalent GyrA-DNA complex that cannot be resolved, thus promoting breakage of plasmid and chromosomal DNA. DNA breakage requires hydrolyzable ATP. Toxicity is inhibited by labile antitoxin CcdA, which blocks the activity of CcdB; CcdA also removes bound CcdB protein from the CcdB-GyrA complex by forming a CcdA-CcdB complex, a process termed rejuvenation. Also acts to inhibit partitioning of the chromosomal DNA. Functions as a transcriptional corepressor for the ccdAB operon, repression also requires CcdA.<ref>PMID:6327993</ref> <ref>PMID:2651399</ref> <ref>PMID:6308648</ref> <ref>PMID:2615761</ref> <ref>PMID:1324324</ref> <ref>PMID:8604132</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/vu/2vub_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=2vub ConSurf].
<div style="clear:both"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Bahasi, E M.]]
[[Category: Bahasi EM]]
[[Category: Couturier, M.]]
[[Category: Couturier M]]
[[Category: Dao-Thi, M H.]]
[[Category: Dao-Thi M-H]]
[[Category: Liddington, R.]]
[[Category: Liddington R]]
[[Category: Loris, R.]]
[[Category: Loris R]]
[[Category: Melderen, L Van.]]
[[Category: Poortmans F]]
[[Category: Poortmans, F.]]
[[Category: Van Melderen L]]
[[Category: Wyns, L.]]
[[Category: Wyns L]]
[[Category: CL]]
[[Category: ccdb]]
[[Category: plasmid]]
[[Category: topoisomerase poison]]
 
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