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==CCDB, A TOPOISOMERASE POISON FROM ESCHERICHIA COLI==
==CCDB, A TOPOISOMERASE POISON FROM ESCHERICHIA COLI==
<StructureSection load='4vub' size='340' side='right' caption='[[4vub]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
<StructureSection load='4vub' size='340' side='right'caption='[[4vub]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4vub]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4VUB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4VUB FirstGlance]. <br>
<table><tr><td colspan='2'>[[4vub]] is a 1 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=4VUB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4VUB FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.45&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CCDB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4vub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4vub OCA], [http://pdbe.org/4vub PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4vub RCSB], [http://www.ebi.ac.uk/pdbsum/4vub PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4vub ProSAT]</span></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=4vub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4vub OCA], [https://pdbe.org/4vub PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4vub RCSB], [https://www.ebi.ac.uk/pdbsum/4vub PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4vub ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://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>
[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 ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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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=4vub ConSurf].
</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=4vub ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.
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:9917404<ref>PMID:9917404</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4vub" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Bacillus coli migula 1895]]
[[Category: Escherichia coli]]
[[Category: Bahasi, E M]]
[[Category: Large Structures]]
[[Category: Couturier, M]]
[[Category: Bahasi EM]]
[[Category: Dao-Thi, M H]]
[[Category: Couturier M]]
[[Category: Liddington, R]]
[[Category: Dao-Thi M-H]]
[[Category: Loris, R]]
[[Category: Liddington R]]
[[Category: Melderen, L Van]]
[[Category: Loris R]]
[[Category: Poortmans, F]]
[[Category: Poortmans F]]
[[Category: Wyns, L]]
[[Category: Van Melderen L]]
[[Category: Ccdb]]
[[Category: Wyns L]]
[[Category: Plasmid]]
[[Category: Plasmid addiction]]
[[Category: Topoisomerase poison]]
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