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Literature summary for 2.7.1.176 extracted from

  • Mutschler, H.; Gebhardt, M.; Shoeman, R.L.; Meinhart, A.
    A novel mechanism of programmed cell death in bacteria by toxin-antitoxin systems corrupts peptidoglycan synthesis (2011), PLoS Biol., 9, e1001033.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
gene pezT, DNA and amino acid sequence determination and analysis, expression of truncated variant PezTDELTAC242 in Escherichia coli strain BL21(DE3) Escherichia coli
gene pezT, DNA and amino acid sequence determination and analysis, expression of truncated variant PezTDELTAC242 in Escherichia coli strain BL21(DE3) Streptococcus pyogenes
gene pezT, DNA and amino acid sequence determination and analysis, expression of truncated variant PezTDELTAC242 in Escherichia coli strain BL21(DE3) Streptococcus pneumoniae

Crystallization (Commentary)

Crystallization (Comment) Organism
analysis of the crystal structure of the epsilon/zeta toxin-antitoxin complex bound to UDP-N-acetyl-D-glucosamine at 2.7 A resolution Streptococcus pyogenes

Protein Variants

Protein Variants Comment Organism
D66T site-directed mutagenesis, a nontoxicPezT variant, no bulge formation or lysis after induction of PezT D66T Escherichia coli
D66T site-directed mutagenesis, a nontoxicPezT variant, no bulge formation or lysis after induction of PezT D66T Streptococcus pyogenes
D66T site-directed mutagenesis, a nontoxicPezT variant, no bulge formation or lysis after induction of PezT D66T Streptococcus pneumoniae
additional information construction of truncated variant PezTDELTAC242 , the variant does not accumulate any spontaneous mutations and still retains the toxic phenotype Escherichia coli
additional information construction of truncated variant PezTDELTAC242 , the variant does not accumulate any spontaneous mutations and still retains the toxic phenotype Streptococcus pyogenes
additional information construction of truncated variant PezTDELTAC242 , the variant does not accumulate any spontaneous mutations and still retains the toxic phenotype Streptococcus pneumoniae

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Escherichia coli
Mg2+ required Streptococcus pyogenes
Mg2+ required Streptococcus pneumoniae

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + UDP-N-acetyl-D-glucosamine Escherichia coli the kinase activity is responsible for the toxic function in vivo, because the phosphorylated product inhibits MurA, the enzyme responsible for the first step of peptidoglycan synthesis in bacteria, mechanism, overview ADP + UDP-N-acetyl-D-glucosamine 3'-phosphate
-
?
ATP + UDP-N-acetyl-D-glucosamine Streptococcus pyogenes the kinase activity is responsible for the toxic function in vivo, because the phosphorylated product inhibits MurA, the enzyme responsible for the first step of peptidoglycan synthesis in bacteria, mechanism, overview ADP + UDP-N-acetyl-D-glucosamine 3'-phosphate
-
?
ATP + UDP-N-acetyl-D-glucosamine Streptococcus pneumoniae the kinase activity is responsible for the toxic function in vivo, because the phosphorylated product inhibits MurA, the enzyme responsible for the first step of peptidoglycan synthesis in bacteria, mechanism, overview ADP + UDP-N-acetyl-D-glucosamine 3'-phosphate
-
?

Organism

Organism UniProt Comment Textmining
Escherichia coli
-
-
-
Streptococcus pneumoniae Q97QZ1 gene pezT
-
Streptococcus pyogenes Q54944 gene pezT
-

Purification (Commentary)

Purification (Comment) Organism
recombinant truncated variant PezTDELTAC242 from Escherichia coli strain BL21(DE3) Escherichia coli
recombinant truncated variant PezTDELTAC242 from Escherichia coli strain BL21(DE3) Streptococcus pyogenes
recombinant truncated variant PezTDELTAC242 from Escherichia coli strain BL21(DE3) Streptococcus pneumoniae

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + UDP-N-acetyl-D-glucosamine the kinase activity is responsible for the toxic function in vivo, because the phosphorylated product inhibits MurA, the enzyme responsible for the first step of peptidoglycan synthesis in bacteria, mechanism, overview Escherichia coli ADP + UDP-N-acetyl-D-glucosamine 3'-phosphate
-
?
ATP + UDP-N-acetyl-D-glucosamine the kinase activity is responsible for the toxic function in vivo, because the phosphorylated product inhibits MurA, the enzyme responsible for the first step of peptidoglycan synthesis in bacteria, mechanism, overview Streptococcus pyogenes ADP + UDP-N-acetyl-D-glucosamine 3'-phosphate
-
?
ATP + UDP-N-acetyl-D-glucosamine the kinase activity is responsible for the toxic function in vivo, because the phosphorylated product inhibits MurA, the enzyme responsible for the first step of peptidoglycan synthesis in bacteria, mechanism, overview Streptococcus pneumoniae ADP + UDP-N-acetyl-D-glucosamine 3'-phosphate
-
?
ATP + UDP-N-acetyl-D-glucosamine enzyme-substrate interaction analysis, overview. PezT activity is specific for the presence of the 2'-N-acetyl group on the sugar moiety and the stereoisomeric form of UDP-N-acetyl-D-glucosamine, selectivity for UDP–glucose and UDP-N-acetylgalactosamine is dramatically reduced Escherichia coli ADP + UDP-N-acetyl-D-glucosamine 3'-phosphate
-
?
ATP + UDP-N-acetyl-D-glucosamine enzyme-substrate interaction analysis, overview. PezT activity is specific for the presence of the 2'-N-acetyl group on the sugar moiety and the stereoisomeric form of UDP-N-acetyl-D-glucosamine, selectivity for UDP–glucose and UDP-N-acetylgalactosamine is dramatically reduced Streptococcus pneumoniae ADP + UDP-N-acetyl-D-glucosamine 3'-phosphate
-
?
ATP + UDP-N-acetyl-D-glucosamine enzyme-substrate interaction analysis, overview. PezT activity is specific for the presence of the 2'-N-acetyl group on the sugar moiety and the stereoisomeric form of UDP-N-acetyl-D-glucosamine, selectivity for UDP–glucose and UDP-N-acetylgalactosamine is dramatically reduced. UDP-N-acetyl-D-glucosamine binds to a deep cleft at the molecular surface of the zeta toxin. The side chain group of Asp67 forms a hydrogen bond to the 3'-hydroxyl group of the amino sugar moiety of the substrate Streptococcus pyogenes ADP + UDP-N-acetyl-D-glucosamine 3'-phosphate UDP-N-acetyl-D-glucosamine 3'-phosphate enriches during PezT poisoning in vivo and inhibits peptidoglycan synthesis ?

Synonyms

Synonyms Comment Organism
PezT
-
Escherichia coli
PezT
-
Streptococcus pyogenes
PezT
-
Streptococcus pneumoniae
zeta toxin
-
Escherichia coli
zeta toxin
-
Streptococcus pyogenes
zeta toxin
-
Streptococcus pneumoniae

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
assay at Escherichia coli
25
-
assay at Streptococcus pyogenes
25
-
assay at Streptococcus pneumoniae

Cofactor

Cofactor Comment Organism Structure
ATP dependent on Escherichia coli
ATP dependent on Streptococcus pyogenes
ATP dependent on Streptococcus pneumoniae

General Information

General Information Comment Organism
evolution most genomes of bacteria contain toxin-antitoxin systems. These gene systems encode a toxic protein and its cognate antitoxin. Members of the epsilon/zeta toxin-antitoxin family are found throughout the genomes of pathogenic bacteria Escherichia coli
evolution most genomes of bacteria contain toxin-antitoxin systems. These gene systems encode a toxic protein and its cognate antitoxin. Members of the epsilon/zeta toxin-antitoxin family are found throughout the genomes of pathogenic bacteria Streptococcus pyogenes
evolution most genomes of bacteria contain toxin-antitoxin systems. These gene systems encode a toxic protein and its cognate antitoxin. Members of the epsilon/zeta toxin-antitoxin family are found throughout the genomes of pathogenic bacteria Streptococcus pneumoniae
metabolism mechanism used by zeta toxins to induce programmed cell death in bacteria, overview Escherichia coli
metabolism mechanism used by zeta toxins to induce programmed cell death in bacteria, overview Streptococcus pyogenes
metabolism mechanism used by zeta toxins to induce programmed cell death in bacteria, overview Streptococcus pneumoniae
additional information slow growth protects cells from toxin-induced autolysis Streptococcus pyogenes
physiological function the toxin-antitoxin system is not only able to stabilize resistance plasmids but also to promote virulence. It is linked with numerous functions, including growth modulation, genome maintenance, and stress response. Upon antitoxin degradation, the toxin induces cell stasis or death. zeta Toxins are kinases that poison bacteria through global inhibition of peptidoglycan synthesis. zeta Toxins in general phosphorylate the ubiquitous peptidoglycan precursor uridine diphosphate-N-acetylglucosamine, and this activity is counteracted by binding of antitoxin. Mechanism used by zeta toxins to induce programmed cell death in bacteria, overview. PezT phosphorylates the cell wall precursor and inhibits cell wall synthesis Escherichia coli
physiological function the toxin-antitoxin system is not only able to stabilize resistance plasmids but also to promote virulence. It is linked with numerous functions, including growth modulation, genome maintenance, and stress response. Upon antitoxin degradation, the toxin induces cell stasis or death. zeta Toxins are kinases that poison bacteria through global inhibition of peptidoglycan synthesis. zeta Toxins in general phosphorylate the ubiquitous peptidoglycan precursor uridine diphosphate-N-acetylglucosamine, and this activity is counteracted by binding of antitoxin. Mechanism used by zeta toxins to induce programmed cell death in bacteria, overview. PezT phosphorylates the cell wall precursor and inhibits cell wall synthesis Streptococcus pyogenes
physiological function the toxin-antitoxin system is not only able to stabilize resistance plasmids but also to promote virulence. It is linked with numerous functions, including growth modulation, genome maintenance, and stress response. Upon antitoxin degradation, the toxin induces cell stasis or death. zeta Toxins are kinases that poison bacteria through global inhibition of peptidoglycan synthesis. zeta Toxins in general phosphorylate the ubiquitous peptidoglycan precursor uridine diphosphate-N-acetylglucosamine, and this activity is counteracted by binding of antitoxin. Mechanism used by zeta toxins to induce programmed cell death in bacteria, overview. PezT phosphorylates the cell wall precursor and inhibits cell wall synthesis Streptococcus pneumoniae