2p5t

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==Molecular and structural characterization of the PezAT chromosomal toxin-antitoxin system of the human pathogen Streptococcus pneumoniae==
==Molecular and structural characterization of the PezAT chromosomal toxin-antitoxin system of the human pathogen Streptococcus pneumoniae==
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<StructureSection load='2p5t' size='340' side='right' caption='[[2p5t]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
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<StructureSection load='2p5t' size='340' side='right'caption='[[2p5t]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[2p5t]] is a 9 chain structure with sequence from [http://en.wikipedia.org/wiki/"diplococcus_pneumoniae"_(klein_1884)_weichselbaum_1886 "diplococcus pneumoniae" (klein 1884) weichselbaum 1886] and [http://en.wikipedia.org/wiki/Strpn Strpn]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P5T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2P5T FirstGlance]. <br>
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<table><tr><td colspan='2'>[[2p5t]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae] and [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_TIGR4 Streptococcus pneumoniae TIGR4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P5T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2P5T FirstGlance]. <br>
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</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1gvn|1gvn]]</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2p5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p5t OCA], [https://pdbe.org/2p5t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2p5t RCSB], [https://www.ebi.ac.uk/pdbsum/2p5t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2p5t ProSAT]</span></td></tr>
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<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=2p5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p5t OCA], [http://pdbe.org/2p5t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2p5t RCSB], [http://www.ebi.ac.uk/pdbsum/2p5t PDBsum]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/PEZT_STRPN PEZT_STRPN]] Toxic component of a toxin-antitoxin (TA) module. Phosphorylates UDP-N-acetyl-D-glucosamine (UNAG) on the 3'-hydroxyl group of the N-acetyl-D-glucosamine moiety, yielding UNAG-3P. UNAG-3P inhibits MurA, the first committed step in cell wall synthesis, which is then blocked. Upon expression in E.coli results in decreased cell growth and viability, followed 3 hours later by growth restoration; the toxic effect and phosphorylation of UNAG are neutralized by coexpression with cognate antitoxin PezA. A mutant lacking the last 11 residues is stably maintained in E.coli, unlike the wild-type which undergoes spontaneous mutation. Expression of the deletion mutant in rapidly growing liquid cultures leads to cell bulging, permeabilization and massive lysis by 1 hour. Cells that survive are not able to undergo cytokinesis. Expression in slowly growing cells leads to bulging but not lysis. Acts as a corepressor of its own operon with PezA; it is not clear if it binds DNA alone. [[http://www.uniprot.org/uniprot/PEZA_STRPN PEZA_STRPN]] Antitoxin component of a toxin-antitoxin (TA) module. Upon expression in E.coli neutralizes the toxic effect of cognate toxin PezT. Represses transcription of its own operon, PezT acts as a corepressor, considerably increasing repression.<ref>PMID:17488720</ref> <ref>PMID:21445328</ref>
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[https://www.uniprot.org/uniprot/PEZA_STRPN PEZA_STRPN] Antitoxin component of a toxin-antitoxin (TA) module. Upon expression in E.coli neutralizes the toxic effect of cognate toxin PezT. Represses transcription of its own operon, PezT acts as a corepressor, considerably increasing repression.<ref>PMID:17488720</ref> <ref>PMID:21445328</ref>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
<jmolCheckbox>
<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p5/2p5t_consurf.spt"</scriptWhenChecked>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p5/2p5t_consurf.spt"</scriptWhenChecked>
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
<text>to colour the structure by Evolutionary Conservation</text>
<text>to colour the structure by Evolutionary Conservation</text>
</jmolCheckbox>
</jmolCheckbox>
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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/chain_selection.php?pdb_ID=2ata ConSurf].
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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=2p5t ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
 
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== Publication Abstract from PubMed ==
 
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The chromosomal pezT gene of the Gram-positive pathogen Streptococcus pneumoniae encodes a protein that is homologous to the zeta toxin of the Streptococcus pyogenes plasmid pSM19035-encoded epsilon-zeta toxin-antitoxin system. Overexpression of pezT in Escherichia coli led to severe growth inhibition from which the bacteria recovered approximately 3 h after induction of expression. The toxicity of PezT was counteracted by PezA, which is encoded immediately upstream of pezT and shares weak sequence similarities in the C-terminal region with the epsilon antitoxin. The pezAT genes form a bicistronic operon that is co-transcribed from a sigma(70)-like promoter upstream of pezA and is negatively autoregulated with PezA functioning as a transcriptional repressor and PezT as a co-repressor. Both PezA and the non-toxic PezA(2)PezT(2) protein complex bind to a palindrome sequence that overlaps the promoter. This differs from the epsilon-zeta system in which epsilon functions solely as the antitoxin and transcriptional regulation is carried out by another protein designated omega. Results from site-directed mutagenesis experiments demonstrated that the toxicity of PezT is dependent on a highly conserved phosphoryltransferase active site and an ATP/GTP nucleotide binding site. In the PezA(2)PezT(2) complex, PezA neutralizes the toxicity of PezT by blocking the nucleotide binding site through steric hindrance.
 
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Molecular and structural characterization of the PezAT chromosomal toxin-antitoxin system of the human pathogen Streptococcus pneumoniae.,Khoo SK, Loll B, Chan WT, Shoeman RL, Ngoo L, Yeo CC, Meinhart A J Biol Chem. 2007 Jul 6;282(27):19606-18. Epub 2007 May 8. PMID:17488720<ref>PMID:17488720</ref>
 
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
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</div>
 
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<div class="pdbe-citations 2p5t" style="background-color:#fffaf0;"></div>
 
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Strpn]]
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[[Category: Large Structures]]
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[[Category: Loll, B]]
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[[Category: Streptococcus pneumoniae]]
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[[Category: Meinhart, A]]
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[[Category: Streptococcus pneumoniae TIGR4]]
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[[Category: Helix-turn-helix motif]]
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[[Category: Loll B]]
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[[Category: Phosphoryltransferase]]
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[[Category: Meinhart A]]
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[[Category: Postsegregational killing system]]
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[[Category: Transcription regulator]]
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Current revision

Molecular and structural characterization of the PezAT chromosomal toxin-antitoxin system of the human pathogen Streptococcus pneumoniae

PDB ID 2p5t

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