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==CCDB, A TOPOISOMERASE POISON FROM E. COLI==
==CCDB, A TOPOISOMERASE POISON FROM E. COLI==
<StructureSection load='3vub' size='340' side='right' caption='[[3vub]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
<StructureSection load='3vub' size='340' side='right'caption='[[3vub]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3vub]] 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=3VUB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VUB FirstGlance]. <br>
<table><tr><td colspan='2'>[[3vub]] 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=3VUB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VUB 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]] 1.4&#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=3vub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vub OCA], [http://pdbe.org/3vub PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3vub RCSB], [http://www.ebi.ac.uk/pdbsum/3vub PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3vub 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=3vub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vub OCA], [https://pdbe.org/3vub PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vub RCSB], [https://www.ebi.ac.uk/pdbsum/3vub PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vub 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=3vub 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=3vub 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 3vub" 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: Topoisomerase poison]]

Latest revision as of 13:35, 1 March 2024

CCDB, A TOPOISOMERASE POISON FROM E. COLICCDB, A TOPOISOMERASE POISON FROM E. COLI

Structural highlights

3vub is a 1 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.4Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.[1] [2] [3] [4] [5] [6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

  1. ↑ Miki T, Yoshioka K, Horiuchi T. Control of cell division by sex factor F in Escherichia coli. I. The 42.84-43.6 F segment couples cell division of the host bacteria with replication of plasmid DNA. J Mol Biol. 1984 Apr 25;174(4):605-25. PMID:6327993
  2. ↑ Tam JE, Kline BC. Control of the ccd operon in plasmid F. J Bacteriol. 1989 May;171(5):2353-60. PMID:2651399
  3. ↑ Ogura T, Hiraga S. Mini-F plasmid genes that couple host cell division to plasmid proliferation. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4784-8. PMID:6308648
  4. ↑ Tam JE, Kline BC. The F plasmid ccd autorepressor is a complex of CcdA and CcdB proteins. Mol Gen Genet. 1989 Oct;219(1-2):26-32. PMID:2615761
  5. ↑ Bernard P, Couturier M. Cell killing by the F plasmid CcdB protein involves poisoning of DNA-topoisomerase II complexes. J Mol Biol. 1992 Aug 5;226(3):735-45. PMID:1324324
  6. ↑ Maki S, Takiguchi S, Horiuchi T, Sekimizu K, Miki T. Partner switching mechanisms in inactivation and rejuvenation of Escherichia coli DNA gyrase by F plasmid proteins LetD (CcdB) and LetA (CcdA). J Mol Biol. 1996 Mar 1;256(3):473-82. PMID:8604132 doi:http://dx.doi.org/10.1006/jmbi.1996.0102

3vub, resolution 1.40Å

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