2p5t

From Proteopedia

(Difference between revisions)

Revision as of 07:54, 2 March 2022

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

Structural highlights

2p5t is a 9 chain structure with sequence from "diplococcus_pneumoniae"_(klein_1884)_weichselbaum_1886 "diplococcus pneumoniae" (klein 1884) weichselbaum 1886 and Strpn. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Related:	1gvn
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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. [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.^[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 PubMed

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.

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Khoo SK, Loll B, Chan WT, Shoeman RL, Ngoo L, Yeo CC, Meinhart A. Molecular and structural characterization of the PezAT chromosomal toxin-antitoxin system of the human pathogen Streptococcus pneumoniae. J Biol Chem. 2007 Jul 6;282(27):19606-18. Epub 2007 May 8. PMID:17488720 doi:10.1074/jbc.M701703200
↑ Mutschler H, Gebhardt M, Shoeman RL, Meinhart A. A novel mechanism of programmed cell death in bacteria by toxin-antitoxin systems corrupts peptidoglycan synthesis. PLoS Biol. 2011 Mar;9(3):e1001033. Epub 2011 Mar 22. PMID:21445328 doi:10.1371/journal.pbio.1001033
↑ Khoo SK, Loll B, Chan WT, Shoeman RL, Ngoo L, Yeo CC, Meinhart A. Molecular and structural characterization of the PezAT chromosomal toxin-antitoxin system of the human pathogen Streptococcus pneumoniae. J Biol Chem. 2007 Jul 6;282(27):19606-18. Epub 2007 May 8. PMID:17488720 doi:10.1074/jbc.M701703200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2p5t"

@@ Line 3: / Line 3: @@
 <StructureSection load='2p5t' size='340' side='right'caption='[[2p5t]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<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://proteopedia.org/fgij/fg.htm?mol=2P5T FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2p5t]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/"diplococcus_pneumoniae"_(klein_1884)_weichselbaum_1886 "diplococcus pneumoniae" (klein 1884) weichselbaum 1886] and [https://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 [https://proteopedia.org/fgij/fg.htm?mol=2P5T FirstGlance]. <br>
 </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>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1gvn|1gvn]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1gvn|1gvn]]</div></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/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], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2p5t 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=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>
 </table>
 == Function ==
-[[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>
+[[https://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. [[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 ==
 [[Image:Consurf_key_small.gif|200px|right]]

2p5t

From Proteopedia

Revision as of 07:54, 2 March 2022

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

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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