3.4.24.83: anthrax lethal factor endopeptidase
This is an abbreviated version!
For detailed information about anthrax lethal factor endopeptidase, go to the full flat file.
Word Map on EC 3.4.24.83
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3.4.24.83
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edema
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spore
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intoxication
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endosomal
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exotoxin
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metalloprotease
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inhalation
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inflammasome
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endocytosis
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toxin-induced
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anti-pa
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heptameric
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caspase-1
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sterne
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furin
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mapkks
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lt-induced
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tripartite
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diphtheria
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toxin-mediated
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spore-forming
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pyroptosis
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toxemia
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ring-shaped
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receptor-bound
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toxin-neutralizing
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zinc-dependent
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molecular biology
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cytolysis
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pa-binding
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medicine
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mkk
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bioterrorism
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diagnostics
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toxin-sensitive
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synthesis
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postexposure
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cell-binding
- 3.4.24.83
-
edema
- spore
-
intoxication
- endosomal
-
exotoxin
- metalloprotease
-
inhalation
- inflammasome
-
endocytosis
-
toxin-induced
-
anti-pa
-
heptameric
- caspase-1
- sterne
- furin
- mapkks
-
lt-induced
-
tripartite
- diphtheria
-
toxin-mediated
-
spore-forming
-
pyroptosis
- toxemia
-
ring-shaped
-
receptor-bound
-
toxin-neutralizing
-
zinc-dependent
- molecular biology
-
cytolysis
-
pa-binding
- medicine
- mkk
-
bioterrorism
- diagnostics
-
toxin-sensitive
- synthesis
-
postexposure
-
cell-binding
Reaction
Preferred amino acids around the cleavage site can be denoted BBBBxHx-/-H, in which B denotes Arg or Lys, H denotes a hydrophobic amino acid, and x is any amino acid. The only known protein substrates are mitogen-activated protein (MAP) kinase kinases =
Synonyms
anthrax lethal factor, anthrax lethal factor protease, anthrax lethal toxin, anthrax LF, anthrax toxin lethal factor, Bacillus anthracis lethal toxin, lethal factor, lethal factor of anthrax toxin, lethal toxin, LeTx, LF, LTx
ECTree
3.4.24.83 anthrax lethal factor endopeptidaseAdvanced search results
results (
results (Engineering
Engineering on EC 3.4.24.83 - anthrax lethal factor endopeptidase
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
E269A
the mutant shows strongly increased cleavage ability for mitogen-activated protein kinase kinase-1 and reduced activity with mitogen-activated protein kinase kinase-6 compared to the wild type enzyme
E539R
the mutant shows slightly increased cleavage ability for mitogen-activated protein kinase kinase-1 and reduced activity with mitogen-activated protein kinase kinase-6 compared to the wild type enzyme
H690A
K518E/E682G
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mutation in anthrax lethal factor, mutant is defective at causing pyroptosis in RAW 264.7 cells and at activating the Nlrp1b inflammasome in a heterologous expression system. LF-K518E /E682G does not exhibit an overall impairment of function and LF-K518E /E682G efficiently kills melanoma cells
L259A
the mutant cleaves MEK1 about 2fold less efficiently than the wild type enzyme
L431A
the mutant shows slightly increased cleavage ability for mitogen-activated protein kinase kinase-6 compared to the wild type enzyme
M264A
the mutant cleaves MEK1 2.5fold less efficiently than the wild type enzyme
R263A
the mutant shows reduced cleavage ability for mitogen-activated protein kinase kinase-1 compared to the wild type enzyme
R491E
the mutant cleaves MEK1 about 2fold less efficiently than the wild type enzyme
W271A
the mutation completely abolishes cleavage ability of mitogen-activated protein kinase kinase-6 but has no effect on the ability to cleave MEK1. The mutant blocks ERK phosphorylation and growth in a melanoma cell line, suggesting that it may provide a highly selective inhibitor of MEK1/2 for use as a cancer therapeutic
Y268A
the mutant cleaves MEK1 6fold less efficiently than the wild type enzyme
additional information
additional information
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effects of anthrax lethal toxin on human primary keratinocytes are investigated. Cells are resistant to LeTx-triggered cytotoxicity, even though all the MEK (MEK1 through 7), except MEK5, are cleaved in these cells. Over the 24 h time course of the study, the levels of two pro-inflammatory molecules, interleukin-6 and granulocyte-macrophage colony stimulating factor (GM-CSF), decline, but the production of RANTES, a known chemoattractant for multiple types of immune cells, increases
additional information
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in order to examine the role of protective antigen a lethal factor (LFn) fusion protein bearing two epitopes from Ova, one restricted by MHC-II and one restricted by MHC-I is generated. This single LFn fusion protein is capable of stimulating both ovalbumin-specific CD4+ and ovalbumin-specific CD8+ T-cell responses in mice
additional information
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intranasal instillationin a mouse model of pulmonary anthrax of a Bacillus anthracis strain RPLC2 bearing inactive lethal toxin (double mutant) lethal toxin stimulates cytokine production (IL-6 and KC, mouse orthologue of IL-8) and polymorphonuclear neutrophils recruitment in lungs. These responses are repressed by a prior instillation of an lethal toxin preparation. In contrast, instillation of a Bacillus anthracis strain expressing active lethal toxin represses lung inflammation. The inhibitory effects of lethal toxin on cytokine production are associated with an alteration of ERK and p38-MAPK phosphorylation, but not JNK phosphorylation. Although NF-kappaB is essential for IL-8 expression, lethal toxin downregulates this expression without interfering with NF-kappaB activation in epithelial cells. Lethal toxin selectively prevents histone H3 phosphorylation at Ser 10 and recruitment of the p65 subunit of NF-kappaB at the IL-8 and KC promoters
additional information
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it is investigated whether lethal factor (LFn) fusion proteins and protective antigen can also be used to deliver antigen to the MHC-II pathway for the stimulation of antigen-specific CD4+ T-cells. A CD4+ T-cell epitope from chicken ovalbumin is fused to nontoxic LFn and demonstrates that this recombinant protein induces an ovalbumin-specific CD4+ T-cell response both in vitro and in mice
additional information
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non-specific furin cleavage sequence (164RKKR167) of the protective antigen of anthrax toxin is substituted by the cleavage sequence for gelatinase class of matrix metalloproteinase (164GPLGMLSQ171) to prevent non-specific action and enhance target specific action in endothelial cells
additional information
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the responses of various murine dendritic cells to anthrax lethal toxin is investigated: Using a variety of knockout mice, it is shown that depending on the mouse strain, death of bone marrow-derived dendritic cells and macrophages is mediated either by a fast Nalp1b, a member of the NOD-like receptor family, and caspase-1-dependent, or by a slow caspase-1-independent pathway that is triggered by the impairment of MEK1/2 pathways. Caspase-1-independent death is observed in cells of different genetic backgrounds and interestingly occurs only in immature dendritic cells. Maturation, triggered by different types of stimuli, leads to full protection of dendritic cells
additional information
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construction of fusion protein of the anthrax toxin lethal factor N-terminal domain LFn, residues 1-254, with beta-lactamase
additional information
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preparation of semisynthetic protective antigen-binding domain of anthrax lethal factor, LFN, by native chemical ligation of synthetic LFN residues 14-28 thioester with recombinant N29C-LFN residues 29-263 and comparison with two variants containing alterations in residues 14-28 of the N-terminal region. An analogue with three positively charged residues and an acetylated N-terminus, blocks ion conductance more efficiently than the control analogue, which lacks charged residues in the N-terminal segment. The semisynthesis platform allows for investigation of the interaction of the pore with its substrates
