Information on EC 3.4.24.83 - anthrax lethal factor endopeptidase

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The expected taxonomic range for this enzyme is: Bacillus

EC NUMBER
COMMENTARY hide
3.4.24.83
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RECOMMENDED NAME
GeneOntology No.
anthrax lethal factor endopeptidase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
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
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
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CAS REGISTRY NUMBER
COMMENTARY hide
477950-41-7
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9001-92-7
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
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about 30% demetallation is observed at pH values close to those found in late endosomes. A substantial proportion of lethal factor molecules may not be in their zinc-bound state prior to translocation
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
83 kDa full-length protective antigen + H2O
20 kDa N-terminal fragment of protective antigen + 63 kDa N-terminal fragment of protective antigen
show the reaction diagram
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?
acetyl-Gly-Tyr-betaAla-RRRRRRRRVLR-4-nitroanilide + H2O
?
show the reaction diagram
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?
acetyl-GYbetaARRRRRRRRVLR-4-nitroanilide + H2O
?
show the reaction diagram
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commercial substrate S-pNA
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?
AcG-Y-betaA-R-R-R-A-R-R-R-R-V-L-R-4-nitroanilide + H2O
AcG-Y-betaA-R-R-R-A-R-R-R-R-V-L-R + 4-nitroaniline
show the reaction diagram
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?
AcM-L-A-R-R-R-P-V-L-P-4-nitroanilide + H2O
AcM-L-A-R-R-R-P-V-L-P + 4-nitroaniline
show the reaction diagram
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-
-
-
?
AcR-R-R-R-V-L-R-4-methylcoumarin-7-amide + H2O
AcR-R-R-R-V-L-R + 7-amino-4-methylcoumarin
show the reaction diagram
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?
AcR-R-R-R-V-L-R-4-nitroanilide + H2O
AcR-R-R-R-V-L-R + 4-nitroaniline
show the reaction diagram
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?
dansyl-RDIRRITLFSLH
?
show the reaction diagram
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i.e. S20D, substrate isolated from phage library
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?
Dsor1 kinase + H2O
?
show the reaction diagram
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Dsor1 is a Drosophila mitogen-activated protein kinase kinase
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?
fluorescein-QRRKKVYPYPME + H2O
fluorescein-QRRKKVYP + YPME
show the reaction diagram
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i.e. LF15, peptide substrate isolated from second-iteration substrate phage library
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?
fluorescence resonance energy transfer peptide MAPKKide + H2O
?
show the reaction diagram
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?
Hep kinase + H2O
?
show the reaction diagram
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Hep (Hemipterous) is a Drosophila mitogen-activated protein kinase kinase
incubation of Hep with anthrax lethal factor generates a product of about 44 kDa
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?
Lic kinase + H2O
?
show the reaction diagram
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Lic (Licorne) is a Drosophila mitogen-activated protein kinase kinase
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?
MAP kinase kinase 3b + H2O
?
show the reaction diagram
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?
Mca-KKPTPIQLN-Dnp + H2O
Mca-KKPTP + IQLN-Dnp
show the reaction diagram
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?
Mca-KKVYPYPMEK-Dnp + H2O
Mca-KKVYP + YPMEK-Dnp
show the reaction diagram
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?
Mca-KKWLMYPLEK-Dnp + H2O
Mca-KKWLM + YPLEK-Dnp
show the reaction diagram
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?
MEK1 + H2O
?
show the reaction diagram
MEK2 + H2O
?
show the reaction diagram
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mitogen-activated protein kinase kinase, cleavage between residues 10-11
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?
mitogen activated protein kinase kinase + H2O
?
show the reaction diagram
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?
mitogen activated protein kinase kinase 1 + H2O
?
show the reaction diagram
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?
mitogen-activated protein kinase + H2O
?
show the reaction diagram
mitogen-activated protein kinase 3 + H2O
?
show the reaction diagram
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?
mitogen-activated protein kinase kinase + H2O
?
show the reaction diagram
mitogen-activated protein kinase kinase 1 + H2O
?
show the reaction diagram
mitogen-activated protein kinase kinase 2 + H2O
?
show the reaction diagram
mitogen-activated protein kinase kinase 3 + H2O
?
show the reaction diagram
mitogen-activated protein kinase kinase 3b + H2O
?
show the reaction diagram
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?
mitogen-activated protein kinase kinase 4 + H2O
?
show the reaction diagram
mitogen-activated protein kinase kinase 6 + H2O
?
show the reaction diagram
mitogen-activated protein kinase kinase 7 + H2O
?
show the reaction diagram
MKK3b + H2O
?
show the reaction diagram
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mitogen-activated protein kinase kinase, cleavage between residues 26-27
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?
MKK4 + H2O
?
show the reaction diagram
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mitogen-activated protein kinase kinase, cleavage between residues 45-46 and 58-59
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?
MKK6b + H2O
?
show the reaction diagram
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mitogen-activated protein kinase kinase, cleavage between residues 14-15
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?
MKK7beta + H2O
?
show the reaction diagram
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mitogen-activated protein kinase kinase, cleavage between residues 44-45 and 76-77
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?
NOD-like receptor protein-1 + H2O
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show the reaction diagram
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lethal factor cleaves rat NOD-like receptor protein Nlrp1. Cleavage is required for toxin-induced inflammasome activation, interleukin IL-1beta release, and macrophage pyroptosis
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?
SKARRKKVYPYPXENFPPSTARPT + H2O
SKARRKKVYP + YPXENFPPSTARPT
show the reaction diagram
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?
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
MAP kinase kinase 3b + H2O
?
show the reaction diagram
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?
Mca-KKPTPIQLN-Dnp + H2O
Mca-KKPTP + IQLN-Dnp
show the reaction diagram
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?
Mca-KKVYPYPMEK-Dnp + H2O
Mca-KKVYP + YPMEK-Dnp
show the reaction diagram
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?
Mca-KKWLMYPLEK-Dnp + H2O
Mca-KKWLM + YPLEK-Dnp
show the reaction diagram
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?
mitogen-activated protein kinase + H2O
?
show the reaction diagram
mitogen-activated protein kinase kinase + H2O
?
show the reaction diagram
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?
mitogen-activated protein kinase kinase 1 + H2O
?
show the reaction diagram
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?
mitogen-activated protein kinase kinase 2 + H2O
?
show the reaction diagram
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-
-
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?
mitogen-activated protein kinase kinase 3 + H2O
?
show the reaction diagram
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?
mitogen-activated protein kinase kinase 4 + H2O
?
show the reaction diagram
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-
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?
mitogen-activated protein kinase kinase 6 + H2O
?
show the reaction diagram
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?
mitogen-activated protein kinase kinase 7 + H2O
?
show the reaction diagram
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?
SKARRKKVYPYPXENFPPSTARPT + H2O
SKARRKKVYP + YPXENFPPSTARPT
show the reaction diagram
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?
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
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activation ability of divalent ions decreases in the follwing order: Zn2+ Ca2+ Mn2+ Mg2+, with Mg2+ completely unable to activate the enzyme
Cu2+
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Cu2+-substituted lethal factor, prepared by direct exchange and by apoprotein reconstitution methodologies, displays a several-fold higher catalytic competence towards chromogenic and fluorogenic lethal factor substrates than native lethal factor. Cu2+ is bound tightly with a dissociation constant in the femtomolar range. The protein-bound metal ion is coordinated to two nitrogen donor atoms, suggesting that Cu2+ binds to both active site histidine residues. Cu2+-substituted lethal factor is capable of killing RAW 264.7 murine macrophage-like cells
Ni2+
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Co2+ is capable to reactivate the apoprotein of lethal factor to a level comparable to that noted for the native zinc enzyme. Co2+-substituted lethal factor is not capable of killing RAW 264.7 murine macrophage-like cells
additional information
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Mg2+ is unable to activate
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(1E,6E)-4-(1,3-dithian-2-ylidene)-1,7-difuran-2-ylhepta-1,6-diene-3,5-dione
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(1Z,6E)-4-(1,3-dithian-2-ylidene)-1,7-difuran-2-ylhepta-1,6-diene-3,5-dione
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(2R)-N4-hydroxy-N1-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide
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inhibitor identified by in silico high-throughput virtual screening protocol
(2S)-6-[(1R)-N-1-(4-fluorophenyl)propan]aminoamino-2-(4-fluoro-3,5-dimethylbenzyl)-N-hydroxyhexanamide
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inhibitor provides protection against lethal infection when administered as a monotherapy. Two doses (10 mg/kg) administered at 2 h and 8 h after spore infection are sufficient to provide a significant survival benefit in infected mice
(2S)-6-[N-1-(4-fluorophenyl)propan]amino-2-[(2R)-2-(4-fluorophenyl)-2-methoxyethyl]-N-hydroxyhexanamide
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inhibitor provides protection against lethal infection when administered as a monotherapy. Two doses (10 mg/kg) administered at 2 h and 8 h after spore infection are sufficient to provide a significant survival benefit in infected mice
(3S)-N-hydroxy-4-methyl-3-([[(2R)-1-(methylamino)-1-oxo-4-phenylbutan-2-yl]amino]methyl)pentanamide
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inhibitor identified by in silico high-throughput virtual screening protocol
(4E)-4-[(2,4-dihydroxyphenyl)methylidene]-1,2,5-thiadiazolidin-3-one
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(5E)-5-(1,3-benzothiazol-2-ylimino)-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid
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(5Z)-3-(4-hydroxyphenyl)-5-[[5-(4-nitrophenyl)furan-2-yl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
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(5Z)-3-(4-methoxyphenyl)-2-thioxo-5-([5-[3-(trifluoromethyl)phenyl]furan-2-yl]methylidene)-1,3-thiazolidin-4-one
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(5Z)-3-(furan-2-ylmethyl)-5-[[5-(3-nitrophenyl)furan-2-yl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
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(5Z)-3-(furan-2-ylmethyl)-5-[[5-(4-nitrophenyl)furan-2-yl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
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(5Z)-5-[(2,4-dihydroxyphenyl)methylidene]-2-thioxoimidazolidin-4-one
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(5Z)-5-[[5-(2-nitrophenyl)furan-2-yl]methylidene]-3-(2-phenylethyl)-2-thioxo-1,3-thiazolidin-4-one
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(5Z)-5-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
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(5Z)-5-[[5-(4-bromo-3-chlorophenyl)furan-2-yl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
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(5Z)-5-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-3-(furan-2-ylmethyl)-2-thioxo-1,3-thiazolidin-4-one
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(5Z)-5-[[5-(4-fluorophenyl)furan-2-yl]methylidene]-3-prop-2-en-1-yl-2-thioxo-1,3-thiazolidin-4-one
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(9E)-N-[2-(2,4,5-trihydroxyphenyl)ethyl]octadec-9-enamide
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(9E)-N-[2-(3,4,5-trihydroxyphenyl)ethyl]octadec-9-enamide
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(9Z)-N-(3,4-dihydroxybenzyl)octadec-9-enamide
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(9Z)-N-[2-(3,4-dihydroxyphenyl)ethyl]octadec-9-enamide
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(D-R)9LPY-CO-NHOH
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(D-R)9VLR-CO-NHOH
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(D-R)9WLM-CO-NHOH
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1-[(1S,2R,3S,4S,6S)-2-amino-6-[(6-amino-2,6-dideoxy-a-D-arabino-hexopyranosyl)oxy]-3,4-dihydroxycyclohexyl]guanidine
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2-([benzyl(ethyl)amino]methyl)-6-iodo-4-methylphenol
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inhibitor identified by in silico high-throughput virtual screening protocol
2-chloro-4-(5-[(Z)-[(3-cyano-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)imino]methyl]furan-2-yl)benzoic acid
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2-chloro-4-(5-[(Z)-[4-oxo-3-(pyridin-3-ylmethyl)-2-thioxo-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl)benzoic acid
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2-chloro-4-[5-[(Z)-(4-oxo-3-prop-2-en-1-yl-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]furan-2-yl]benzoic acid
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2-chloro-4-[[(4Z)-4-[[4-(methylsulfanyl)phenyl]methylidene]-5-oxo-2-phenyl-4,5-dihydro-1H-imidazol-1-yl]sulfamoyl]benzoic acid
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2-chloro-5-(2,5-dimethyl-1H-pyrrol-1-yl)benzoic acid
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2-chloro-5-[(4Z)-3-methyl-4-[[4-(1-methylethyl)phenyl]methylidene]-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
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2-chloro-5-[(4Z)-4-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
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2-chloro-5-[[(4Z)-4-[[4-(methylsulfanyl)phenyl]methylidene]-5-oxo-2-phenylimidazolidin-1-yl]sulfamoyl]benzoic acid
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2-hydroxy-5-(5-[(Z)-[2-imino-4-oxo-3-(1,3-thiazol-2-yl)-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl)benzoic acid
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2-hydroxy-5-[5-[(Z)-[2-imino-3-[imino(methylsulfanyl)methyl]-4-oxo-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl]benzoic acid
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2-thiolacetyl-YPM-amide
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2-[[(2-amino-2-carboxyethyl)sulfanyl]methyl]-5-phenylfuran-3-carboxylic acid
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3,3'-methanediylbis(6-hydroxybenzoic acid)
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3,4-dihydroxy-N'-[(1Z)-(2-hydroxy-5-nitrophenyl)methylidene]benzohydrazide
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3-(5-[(Z)-[1-(3-chlorophenyl)-3,5-dioxopyrazolidin-4-ylidene]methyl]furan-2-yl)benzoic acid
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3-(N-hydroxycarboxamido)-2-isobutylpropanoyl-Trp-methylamide
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inhibitor used for structure-based pharmacopore model
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3-[(5E)-5-[(3-bromo-4-methoxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
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3-[(5Z)-5-[(3-bromo-4-methoxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
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3-[(5Z)-5-[[5-(2-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
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3-[(5Z)-5-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
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3-[(5Z)-5-[[5-(4-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
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4-(2,5-dimethyl-1H-pyrrol-1-yl)-2-hydroxybenzoic acid
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4-(5-[(Z)-[3-(4-nitrophenyl)-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl)benzoic acid
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4-phenylaminocarbonylbis-demethoxycurcumin
-
inhibitory potency is comparable with curcumin, while showing improved solubility and stability
4-[(5Z)-5-[[5-(3-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]butanoic acid
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4-[(5Z)-5-[[5-(4-bromophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]butanoic acid
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4-[5-[(E)-(5-cyano-2-hydroxy-4-methyl-6-oxopyridin-3(6H)-ylidene)methyl]furan-2-yl]benzenesulfonamide
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4-[5-[(Z)-(3-benzyl-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]furan-2-yl]benzoic acid
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4-[5-[(Z)-[4-oxo-2-thioxo-3-[3-(trifluoromethyl)phenyl]-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl]benzoic acid
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4-[[(4-chlorophenyl)carbamoyl]amino]-N-(5-ethyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide
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5-(4-carboxy-3-chlorophenyl)-2-[(Z)-[(3-cyano-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)imino]methyl]furan-3-carboxylic acid
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5-bromo-2-(5-[(Z)-[1-(3-carboxyphenyl)-5-oxo-3-(trifluoromethyl)-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)benzoic acid
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5-bromo-2-(5-[(Z)-[1-(3-carboxyphenyl)-5-oxo-3-(trifluoromethyl)-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]uran-2-yl)benzoic acid
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5-chloro-2-[5-[(E)-(1,5-dioxo-6,7,8,9-tetrahydro-5H-[1]benzothieno[3,2-e][1,3]thiazolo[3,2-a]pyrimidin-2(1H)-ylidene)methyl]furan-2-yl]benzoic acid
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6-S-(3-aminopropyl)-6-thio-beta-D-cyclodextrin
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6-S-(8-aminooctyl)-6-thio-beta-D-cyclodextin
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6-S-[3-(aminomethyl)benzyl]-6-thio-beta-D-cyclodextrin
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6-S-[4-(aminomethyl)benzyl]-6-thio-beta-D-cyclodextrin
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8-[(E)-[[4-(2,3-dihydro-1,3-thiazol-2-ylsulfamoyl)phenyl]imino]methyl]-4H-1,3-benzodioxine-6-carboxylic acid
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acetyl-GYbetaARRRRRRRRVLR-hydroxamate
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AcG-Y-betaA-R-R-R-A-R-R-R-R-V-L-R-4-nitroanilide
-
substrate inhibition
AcM-L-A-R-R-R-P-V-L-P-4-nitroanilide
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substrate inhibition
AcR-R-R-R-V-L-R-4-methylcoumarin-7-amide
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substrate inhibition
AcR-R-R-R-V-L-R-4-nitroanilide
-
substrate inhibition
C-terminal dimer of the protective antigen binding domain of anthrax lethal factor
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C-terminal trimer of the protective antigen binding domain of anthrax lethal factor
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celastrol
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celastrol, a quinine methide triterpene derived from a plant extract used in herbal medicine, inhibits lethal toxin-induced death of RAW264.7 murine macrophages. Celastrol does not prevent cleavage of mitogen activated protein kinase kinase 1. Celastrol confers almost complete protection when it is added up to 1.5 h after intoxication, indicating that it can rescue cells in the late stages of intoxication. Celastrol inhibits the proteasome-dependent degradation of proteins in RAW264.7 cells. Celastrol blocks stimulation of IL-18 processing, indicating that celastrol acts upstream of inflammasome activation
curcumin
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inhibits by both decreasing catalytic capacity and increasing substrate affinity
fluvastatin
-
statins attenuate lethal factor action action. statin treatment maintains macrophage cell viability above 60% of untreated control cells even after 9 h of lethal toxin treatment. Statins decrease mitogen-activated protein kinase cleavage
mevastatin
-
statins attenuate lethal factor action action. statin treatment maintains macrophage cell viability above 60% of untreated control cells even after 9 h of lethal toxin treatment. Statins decrease mitogen-activated protein kinase cleavage
MKARRKKVYP-NHOH
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N'1,N'4-bis[(1E)-(2-hydroxy-5-methylphenyl)methylidene]benzene-1,4-dicarbohydrazide
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N'1-[(1E)-(2-hydroxyphenyl)methylidene]-N'4-[(1Z)-(2-hydroxyphenyl)methylidene]benzene-1,4-dicarbohydrazide
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N'1-[(1E)-(5-fluoro-2-hydroxyphenyl)methylidene]-N'4-[(1Z)-(5-fluoro-2-hydroxyphenyl)methylidene]benzene-1,4-dicarbohydrazide
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N,N''',N'''''',N'''''''''-[[(1R,3S,4S,6R)-4,6-dicarbamimidamidocyclohexane-1,3-diyl]bis(oxybenzene-1,2,4-triyl)]tetraguanidine
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N,N'''-[(1R,3S)-4-(2,4-dicarbamimidamidonaphthalen-1-yl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
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N,N'''-[(1R,3S)-4-(2-amino-1H-benzimidazol-7-yl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
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N,N'''-[(1R,3S,4R,5R,6S)-4-[(2,6-dicarbamimidamido-2,6-dideoxy-a-D-glucopyranosyl)oxy]-5,6-dihydroxycyclohexane-1,3-diyl]diguanidine
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-
N,N'''-[(1R,3S,4R,6R)-4-(2-carbamimidamidophenyl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
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N,N'''-[(1R,3S,4R,6R)-4-(4-carbamimidamidonaphthalen-1-yl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
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N,N'''-[(1R,3S,4R,6R)-4-(4-carbamimidamidophenyl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
-
-
N,N'''-[(1R,3S,4S,6R)-4-(3-carbamimidamidopyridin-2-yl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
-
-
N,N'''-[(1R,3S,4S,6R)-4-(5-carbamimidamidopyridin-2-yl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
-
-
N,N'''-[(1S,2R,3S,4S,6S)-6-[(6-amino-2-carbamimidamido-2,6-dideoxy-a-D-glucopyranosyl)oxy]-3,4-dihydroxycyclohexane-1,2-diyl]diguanidine
-
-
N,N'''-[4-[(1R,2S,4R,5R)-2,4-dicarbamimidamido-5-hydroxycyclohexyl]benzene-1,3-diyl]diguanidine
-
-
N-2-benzyl-N-2-[(4-fluoro-3-methylphenyl)sulfonyl]-N-hydroxy-D-alaninamide
-
-
N-2-[4-(aminomethyl)benzyl]-N-2-[(4-fluoro-3-methylphenyl)sulfonyl]-N-hydroxy-D-alaninamide
-
-
N-hydroxy-4-[2-[(9E)-octadec-9-enoylamino]ethyl]benzamide
-
-
N-hydroxy-4-[[(9Z)-octadec-9-enoylamino]methyl]benzamide
-
-
N-oleoyldopamine
-
uncompetitive inhibition
N-terminal dimer of the protective antigen binding domain of anthrax lethal factor
-
-
-
N-terminal trimer of the protective antigen binding domain of anthrax lethal factor
-
-
-
N2-[(4-fluoro-3-methylphenyl)sulfonyl]-N-hydroxy-N-2-(4-nitrobenzyl)-D-alaninamide
-
-
neamine
-
mixed-type, noncompetitive inhibition
neomycin B
NH4Cl
-
blocks mitogen-activated protein kinase kinase 3 proteolysis in anthrax lethal toxin-treated macrophages
simvastatin
-
statins attenuate lethal factor action action. statin treatment maintains macrophage cell viability above 60% of untreated control cells even after 9 h of lethal toxin treatment. Statins decrease mitogen-activated protein kinase cleavage
verapamil
-
blocks mitogen-activated protein kinase kinase 3 proteolysis in anthrax lethal toxin-treated macrophages
[(5Z)-5-([5-[2-chloro-5-(trifluoromethyl)phenyl]furan-2-yl]methylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
[(5Z)-5-[[5-(2-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
[(5Z)-5-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
[(5Z)-5-[[5-(3-chloro-4-methoxyphenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
[(5Z)-5-[[5-(3-chloro-4-sulfamoylphenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
[(5Z)-5-[[5-(3-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
[(5Z)-5-[[5-(4-bromophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
[(5Z)-5-[[5-(4-chloro-2-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
[(5Z)-5-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
[(5Z)-5-[[5-(4-iodophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
[4-(2,5-dimethyl-1H-pyrrol-1-yl)phenyl]acetic acid
-
-
[4-[(5Z)-5-(furan-2-ylmethylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]phenyl]acetic acid
-
-
[[4-(2,5-dimethyl-1H-pyrrol-1-yl)phenyl]sulfanyl]acetic acid
-
-
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
matrix metalloproteinase
-
matrix-metalloproteinase-activated lethal toxin has much lower in vivo toxicity than wild type toxin
-
matrix metalloproteinase 2
-
-
-
matrix metalloproteinase 9
-
-
-
additional information
-
monoclonal antibodies PA I 3F3-2-2, PA 2II 2F9-1-1, and PA I 6C3-1-1, directed against protective antigen of Bacillus anthracis, enhance lethal toxin activity in vivo
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.073
acetyl-GYbetaARRRRRRRRVLR-4-nitroanilide
-
pH 7.4, 22C, apoprotein reconstituted in presence of Zn2+
-
0.0018
AcG-Y-betaA-R-R-R-A-R-R-R-R-V-L-R-4-nitroanilide
-
-
0.03
AcM-L-A-R-R-R-P-V-L-P-4-nitroanilide
-
-
0.082
AcR-R-R-R-V-L-R-4-methylcoumarin-7-amide
-
-
0.0095
AcR-R-R-R-V-L-R-4-nitroanilide
-
-
0.0023 - 0.042
fluorescein-QRRKKVYPYPME
0.0086
fluorescence resonance energy transfer peptide MAPKKide
-
in 20 mM HEPES, pH 7.4, at 25C
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
21.2
acetyl-GYbetaARRRRRRRRVLR-4-nitroanilide
Bacillus anthracis
-
pH 7.4, 22C, apoprotein reconstituted in presence of Cu2+
-
0.01 - 0.52
fluorescein-QRRKKVYPYPME
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2900
acetyl-GYbetaARRRRRRRRVLR-4-nitroanilide
Bacillus anthracis
-
pH 7.4, 22C, apoprotein reconstituted in presence of Zn2+
206923
0.000025
Mca-KKPTPIQLN-Dnp
Bacillus anthracis
-
in 0.1 M HEPES, pH 7.4 at 37C
169964
0.0013
Mca-KKVYPYPMEK-Dnp
Bacillus anthracis
-
in 0.1 M HEPES, pH 7.4 at 37C
169965
0.0023
Mca-KKWLMYPLEK-Dnp
Bacillus anthracis
-
in 0.1 M HEPES, pH 7.4 at 37C
169966
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0027
(1E,6E)-4-(1,3-dithian-2-ylidene)-1,7-difuran-2-ylhepta-1,6-diene-3,5-dione
0.000000042
(2S)-6-[(1R)-N-1-(4-fluorophenyl)propan]aminoamino-2-(4-fluoro-3,5-dimethylbenzyl)-N-hydroxyhexanamide
-
pH not specified in the publication, temperature not specified in the publication
0.00000033
(2S)-6-[N-1-(4-fluorophenyl)propan]amino-2-[(2R)-2-(4-fluorophenyl)-2-methoxyethyl]-N-hydroxyhexanamide
-
pH not specified in the publication, temperature not specified in the publication
0.0011
(4E)-4-[(2,4-dihydroxyphenyl)methylidene]-1,2,5-thiadiazolidin-3-one
-
-
0.0042
(5E)-5-(1,3-benzothiazol-2-ylimino)-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid
-
-
0.0011
(5Z)-5-[(2,4-dihydroxyphenyl)methylidene]-2-thioxoimidazolidin-4-one
-
-
0.0017
(9E)-N-[2-(3,4,5-trihydroxyphenyl)ethyl]octadec-9-enamide
-
-
0.0022
(9Z)-N-(3,4-dihydroxybenzyl)octadec-9-enamide
-
-
0.003
(9Z)-N-[2-(3,4-dihydroxyphenyl)ethyl]octadec-9-enamide
-
-
0.00000732
(D-R)9LPY-CO-NHOH
-
in 0.1 M HEPES, pH 7.4 at 37C
0.00000145
(D-R)9VLR-CO-NHOH
-
in 0.1 M HEPES, pH 7.4 at 37C
0.00000028
(D-R)9WLM-CO-NHOH
-
in 0.1 M HEPES, pH 7.4 at 37C
0.0024
2-chloro-4-(5-[(Z)-[(3-cyano-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)imino]methyl]furan-2-yl)benzoic acid
-
-
0.0025
2-chloro-4-[[(4Z)-4-[[4-(methylsulfanyl)phenyl]methylidene]-5-oxo-2-phenyl-4,5-dihydro-1H-imidazol-1-yl]sulfamoyl]benzoic acid
-
-
0.0056
2-chloro-5-(2,5-dimethyl-1H-pyrrol-1-yl)benzoic acid
-
-
0.0009
2-chloro-5-[(4Z)-3-methyl-4-[[4-(1-methylethyl)phenyl]methylidene]-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
-
-
0.0021 - 0.0107
2-chloro-5-[(4Z)-4-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
0.0036
2-chloro-5-[[(4Z)-4-[[4-(methylsulfanyl)phenyl]methylidene]-5-oxo-2-phenylimidazolidin-1-yl]sulfamoyl]benzoic acid
-
-
0.0031
2-hydroxy-5-(5-[(Z)-[2-imino-4-oxo-3-(1,3-thiazol-2-yl)-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl)benzoic acid
0.011
2-thiolacetyl-YPM-amide
-
-
0.0029
2-[[(2-amino-2-carboxyethyl)sulfanyl]methyl]-5-phenylfuran-3-carboxylic acid
-
-
0.0024
3,3'-methanediylbis(6-hydroxybenzoic acid)
-
-
0.0054 - 0.0072
3-(5-[(Z)-[1-(3-chlorophenyl)-3,5-dioxopyrazolidin-4-ylidene]methyl]furan-2-yl)benzoic acid
0.0033
3-[(5E)-5-[(3-bromo-4-methoxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
0.0015
4-(2,5-dimethyl-1H-pyrrol-1-yl)-2-hydroxybenzoic acid
-
-
0.0054
4-[5-[(E)-(5-cyano-2-hydroxy-4-methyl-6-oxopyridin-3(6H)-ylidene)methyl]furan-2-yl]benzenesulfonamide
-
-
0.0009
4-[[(4-chlorophenyl)carbamoyl]amino]-N-(5-ethyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide
-
-
0.0024
5-(4-carboxy-3-chlorophenyl)-2-[(Z)-[(3-cyano-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)imino]methyl]furan-3-carboxylic acid
-
-
0.0016
5-bromo-2-(5-[(Z)-[1-(3-carboxyphenyl)-5-oxo-3-(trifluoromethyl)-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)benzoic acid
0.0008 - 0.0011
5-chloro-2-[5-[(E)-(1,5-dioxo-6,7,8,9-tetrahydro-5H-[1]benzothieno[3,2-e][1,3]thiazolo[3,2-a]pyrimidin-2(1H)-ylidene)methyl]furan-2-yl]benzoic acid
0.0018
8-[(E)-[[4-(2,3-dihydro-1,3-thiazol-2-ylsulfamoyl)phenyl]imino]methyl]-4H-1,3-benzodioxine-6-carboxylic acid
-
-
0.000001
acetyl-GYbetaARRRRRRRRVLR-hydroxamate
-
-
0.036
AcG-Y-betaA-R-R-R-A-R-R-R-R-V-L-R-4-nitroanilide
-
-
0.6
AcM-L-A-R-R-R-P-V-L-P-4-nitroanilide
-
-
0.17
AcR-R-R-R-V-L-R-4-methylcoumarin-7-amide
-
-
0.19
AcR-R-R-R-V-L-R-4-nitroanilide
-
-
0.002
GM6001
-
-
0.000001
MKARRKKVYP-NHOH
-
-
0.06
N-hydroxy-4-[2-[(9E)-octadec-9-enoylamino]ethyl]benzamide
-
-
0.0062
N-hydroxy-4-[[(9Z)-octadec-9-enoylamino]methyl]benzamide
-
-
0.003
N-oleoyldopamine
-
-
0.013
neamine
-
in 20 mM HEPES, pH 7.4, at 25C
0.000007 - 0.00028
neomycin B
0.000032
[(5Z)-5-([5-[2-chloro-5-(trifluoromethyl)phenyl]furan-2-yl]methylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
0.0009
[4-(2,5-dimethyl-1H-pyrrol-1-yl)phenyl]acetic acid
-
-
0.0016
[[4-(2,5-dimethyl-1H-pyrrol-1-yl)phenyl]sulfanyl]acetic acid
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.003
(1E,6E)-4-(1,3-dithian-2-ylidene)-1,7-difuran-2-ylhepta-1,6-diene-3,5-dione
0.0102
(2R)-N4-hydroxy-N1-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide
Bacillus anthracis
-
pH 8.0, 37C
0.0071
(3S)-N-hydroxy-4-methyl-3-([[(2R)-1-(methylamino)-1-oxo-4-phenylbutan-2-yl]amino]methyl)pentanamide
Bacillus anthracis
-
pH 8.0, 37C
0.0034
(4E)-4-[(2,4-dihydroxyphenyl)methylidene]-1,2,5-thiadiazolidin-3-one
Bacillus anthracis
-
-
0.0077
(5E)-5-(1,3-benzothiazol-2-ylimino)-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid
Bacillus anthracis
-
-
0.0377
(5Z)-3-(4-hydroxyphenyl)-5-[[5-(4-nitrophenyl)furan-2-yl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Bacillus anthracis
-
-
0.3
(5Z)-3-(4-methoxyphenyl)-2-thioxo-5-([5-[3-(trifluoromethyl)phenyl]furan-2-yl]methylidene)-1,3-thiazolidin-4-one
Bacillus anthracis
-
-
0.0383
(5Z)-3-(furan-2-ylmethyl)-5-[[5-(3-nitrophenyl)furan-2-yl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Bacillus anthracis
-
-
0.0126
(5Z)-3-(furan-2-ylmethyl)-5-[[5-(4-nitrophenyl)furan-2-yl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Bacillus anthracis
-
-
0.0034
(5Z)-5-[(2,4-dihydroxyphenyl)methylidene]-2-thioxoimidazolidin-4-one
Bacillus anthracis
-
-
0.0319
(5Z)-5-[[5-(2-nitrophenyl)furan-2-yl]methylidene]-3-(2-phenylethyl)-2-thioxo-1,3-thiazolidin-4-one
Bacillus anthracis
-
-
0.0074
(5Z)-5-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Bacillus anthracis
-
-
0.007
(5Z)-5-[[5-(4-bromo-3-chlorophenyl)furan-2-yl]methylidene]-2-thioxo-1,3-thiazolidin-4-one
Bacillus anthracis
-
-
0.15
(5Z)-5-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-3-(furan-2-ylmethyl)-2-thioxo-1,3-thiazolidin-4-one
Bacillus anthracis
-
-
0.05
(5Z)-5-[[5-(4-fluorophenyl)furan-2-yl]methylidene]-3-prop-2-en-1-yl-2-thioxo-1,3-thiazolidin-4-one
Bacillus anthracis
-
-
0.07
(9E)-N-[2-(2,4,5-trihydroxyphenyl)ethyl]octadec-9-enamide
Bacillus anthracis
-
-
0.013
(9E)-N-[2-(3,4,5-trihydroxyphenyl)ethyl]octadec-9-enamide
Bacillus anthracis
-
-
0.015
(9Z)-N-(3,4-dihydroxybenzyl)octadec-9-enamide
0.0007
1-[(1S,2R,3S,4S,6S)-2-amino-6-[(6-amino-2,6-dideoxy-a-D-arabino-hexopyranosyl)oxy]-3,4-dihydroxycyclohexyl]guanidine
Bacillus anthracis
-
-
0.0495
2-([benzyl(ethyl)amino]methyl)-6-iodo-4-methylphenol
Bacillus anthracis
-
pH 8.0, 37C
0.0042
2-chloro-4-(5-[(Z)-[(3-cyano-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)imino]methyl]furan-2-yl)benzoic acid
Bacillus anthracis
-
-
0.0099
2-chloro-4-(5-[(Z)-[4-oxo-3-(pyridin-3-ylmethyl)-2-thioxo-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl)benzoic acid
Bacillus anthracis
-
-
0.0027
2-chloro-4-[5-[(Z)-(4-oxo-3-prop-2-en-1-yl-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]furan-2-yl]benzoic acid
Bacillus anthracis
-
-
0.0036
2-chloro-4-[[(4Z)-4-[[4-(methylsulfanyl)phenyl]methylidene]-5-oxo-2-phenyl-4,5-dihydro-1H-imidazol-1-yl]sulfamoyl]benzoic acid
Bacillus anthracis
-
-
0.0068
2-chloro-5-(2,5-dimethyl-1H-pyrrol-1-yl)benzoic acid
Bacillus anthracis
-
-
0.0079
2-chloro-5-[(4Z)-3-methyl-4-[[4-(1-methylethyl)phenyl]methylidene]-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
Bacillus anthracis
-
-
0.0021 - 0.0107
2-chloro-5-[(4Z)-4-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
0.0025
2-chloro-5-[[(4Z)-4-[[4-(methylsulfanyl)phenyl]methylidene]-5-oxo-2-phenylimidazolidin-1-yl]sulfamoyl]benzoic acid
Bacillus anthracis
-
-
0.0048
2-hydroxy-5-(5-[(Z)-[2-imino-4-oxo-3-(1,3-thiazol-2-yl)-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl)benzoic acid
0.0036
2-[[(2-amino-2-carboxyethyl)sulfanyl]methyl]-5-phenylfuran-3-carboxylic acid
Bacillus anthracis
-
-
0.0031
3,3'-methanediylbis(6-hydroxybenzoic acid)
Bacillus anthracis
-
-
0.2
3,4-dihydroxy-N'-[(1Z)-(2-hydroxy-5-nitrophenyl)methylidene]benzohydrazide
Bacillus anthracis
-
DS-998
0.0083 - 0.0105
3-(5-[(Z)-[1-(3-chlorophenyl)-3,5-dioxopyrazolidin-4-ylidene]methyl]furan-2-yl)benzoic acid
0.0044
3-[(5E)-5-[(3-bromo-4-methoxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
0.0128
3-[(5Z)-5-[[5-(2-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
Bacillus anthracis
-
-
0.0008
3-[(5Z)-5-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
Bacillus anthracis
-
-
0.0027
3-[(5Z)-5-[[5-(4-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
Bacillus anthracis
-
-
0.0043
4-(2,5-dimethyl-1H-pyrrol-1-yl)-2-hydroxybenzoic acid
Bacillus anthracis
-
-
0.0048
4-(5-[(Z)-[3-(4-nitrophenyl)-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl)benzoic acid
Bacillus anthracis
-
-
0.02
4-[(5Z)-5-[[5-(3-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]butanoic acid
Bacillus anthracis
-
-
0.0023
4-[(5Z)-5-[[5-(4-bromophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]butanoic acid
Bacillus anthracis
-
-
0.0083
4-[5-[(E)-(5-cyano-2-hydroxy-4-methyl-6-oxopyridin-3(6H)-ylidene)methyl]furan-2-yl]benzenesulfonamide
Bacillus anthracis
-
-
0.006
4-[5-[(Z)-(3-benzyl-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]furan-2-yl]benzoic acid
Bacillus anthracis
-
-
0.0029
4-[5-[(Z)-[4-oxo-2-thioxo-3-[3-(trifluoromethyl)phenyl]-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl]benzoic acid
Bacillus anthracis
-
-
0.0039
4-[[(4-chlorophenyl)carbamoyl]amino]-N-(5-ethyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide
Bacillus anthracis
-
-
0.0042
5-(4-carboxy-3-chlorophenyl)-2-[(Z)-[(3-cyano-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)imino]methyl]furan-3-carboxylic acid
Bacillus anthracis
-
-
0.0017
5-bromo-2-(5-[(Z)-[1-(3-carboxyphenyl)-5-oxo-3-(trifluoromethyl)-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)benzoic acid
0.0008
5-chloro-2-[5-[(E)-(1,5-dioxo-6,7,8,9-tetrahydro-5H-[1]benzothieno[3,2-e][1,3]thiazolo[3,2-a]pyrimidin-2(1H)-ylidene)methyl]furan-2-yl]benzoic acid
Bacillus anthracis
-
-
0.0029
6-S-(3-aminopropyl)-6-thio-beta-D-cyclodextrin
Bacillus anthracis
-
-
0.0003
6-S-(8-aminooctyl)-6-thio-beta-D-cyclodextin
Bacillus anthracis
-
-
0.0005
6-S-[3-(aminomethyl)benzyl]-6-thio-beta-D-cyclodextrin
Bacillus anthracis
-
-
0.0007
6-S-[4-(aminomethyl)benzyl]-6-thio-beta-D-cyclodextrin
Bacillus anthracis
-
-
0.0093
8-[(E)-[[4-(2,3-dihydro-1,3-thiazol-2-ylsulfamoyl)phenyl]imino]methyl]-4H-1,3-benzodioxine-6-carboxylic acid
Bacillus anthracis
-
-
0.08
N'1,N'4-bis[(1E)-(2-hydroxy-5-methylphenyl)methylidene]benzene-1,4-dicarbohydrazide
Bacillus anthracis
-
-
0.05
N'1-[(1E)-(2-hydroxyphenyl)methylidene]-N'4-[(1Z)-(2-hydroxyphenyl)methylidene]benzene-1,4-dicarbohydrazide
0.00065
N,N''',N'''''',N'''''''''-[[(1R,3S,4S,6R)-4,6-dicarbamimidamidocyclohexane-1,3-diyl]bis(oxybenzene-1,2,4-triyl)]tetraguanidine
Bacillus anthracis
-
-
0.0107
N,N'''-[(1R,3S)-4-(2,4-dicarbamimidamidonaphthalen-1-yl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
Bacillus anthracis
-
-
0.1537
N,N'''-[(1R,3S)-4-(2-amino-1H-benzimidazol-7-yl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
Bacillus anthracis
-
-
0.0007
N,N'''-[(1R,3S,4R,5R,6S)-4-[(2,6-dicarbamimidamido-2,6-dideoxy-a-D-glucopyranosyl)oxy]-5,6-dihydroxycyclohexane-1,3-diyl]diguanidine
Bacillus anthracis
-
-
0.0306
N,N'''-[(1R,3S,4R,6R)-4-(2-carbamimidamidophenyl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
Bacillus anthracis
-
-
0.0314
N,N'''-[(1R,3S,4R,6R)-4-(4-carbamimidamidonaphthalen-1-yl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
Bacillus anthracis
-
-
0.0149
N,N'''-[(1R,3S,4R,6R)-4-(4-carbamimidamidophenyl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
Bacillus anthracis
-
-
0.0041
N,N'''-[(1R,3S,4S,6R)-4-(3-carbamimidamidopyridin-2-yl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
Bacillus anthracis
-
-
0.0066
N,N'''-[(1R,3S,4S,6R)-4-(5-carbamimidamidopyridin-2-yl)-6-hydroxycyclohexane-1,3-diyl]diguanidine
Bacillus anthracis
-
-
0.0005
N,N'''-[(1S,2R,3S,4S,6S)-6-[(6-amino-2-carbamimidamido-2,6-dideoxy-a-D-glucopyranosyl)oxy]-3,4-dihydroxycyclohexane-1,2-diyl]diguanidine
Bacillus anthracis
-
-
0.0006
N,N'''-[4-[(1R,2S,4R,5R)-2,4-dicarbamimidamido-5-hydroxycyclohexyl]benzene-1,3-diyl]diguanidine
Bacillus anthracis
-
-
0.0152
N-2-benzyl-N-2-[(4-fluoro-3-methylphenyl)sulfonyl]-N-hydroxy-D-alaninamide
Bacillus anthracis
-
pH not specified in the publication, temperature not specified in the publication
0.0056
N-2-[4-(aminomethyl)benzyl]-N-2-[(4-fluoro-3-methylphenyl)sulfonyl]-N-hydroxy-D-alaninamide
Bacillus anthracis
-
pH not specified in the publication, temperature not specified in the publication
0.032
N-hydroxy-4-[2-[(9E)-octadec-9-enoylamino]ethyl]benzamide
Bacillus anthracis
-
-
0.042
N-hydroxy-4-[[(9Z)-octadec-9-enoylamino]methyl]benzamide
Bacillus anthracis
-
-
0.015
N-oleoyldopamine
Bacillus anthracis
-
-
0.0149
N2-[(4-fluoro-3-methylphenyl)sulfonyl]-N-hydroxy-N-2-(4-nitrobenzyl)-D-alaninamide
Bacillus anthracis
-
pH not specified in the publication, temperature not specified in the publication
0.0031
[(5Z)-5-[[5-(2-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
Bacillus anthracis
-
-
0.000265
[(5Z)-5-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
Bacillus anthracis
-
-
0.000298
[(5Z)-5-[[5-(3-chloro-4-methoxyphenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
Bacillus anthracis
-
-
0.0091
[(5Z)-5-[[5-(3-chloro-4-sulfamoylphenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
Bacillus anthracis
-
-
0.0031
[(5Z)-5-[[5-(3-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
Bacillus anthracis
-
-
0.00085
[(5Z)-5-[[5-(4-bromophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
Bacillus anthracis
-
-
0.0005
[(5Z)-5-[[5-(4-chloro-2-nitrophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
Bacillus anthracis
-
-
0.0009
[(5Z)-5-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
Bacillus anthracis
-
-
0.0055
[(5Z)-5-[[5-(4-iodophenyl)furan-2-yl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
Bacillus anthracis
-
-
0.0076
[4-(2,5-dimethyl-1H-pyrrol-1-yl)phenyl]acetic acid
Bacillus anthracis
-
-
0.14
[4-[(5Z)-5-(furan-2-ylmethylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]phenyl]acetic acid
Bacillus anthracis
-
-
0.0029
[[4-(2,5-dimethyl-1H-pyrrol-1-yl)phenyl]sulfanyl]acetic acid
Bacillus anthracis
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
1.24
-
pH 7.4, 22C, apoprotein reconstituted in presence of Zn2+
7.12
-
pH 7.4, 22C, apoprotein reconstituted in presence of Cu2+
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4
-
inactive
5.8
-
progressive further loss of activity. Biphasic loss of activity upon acidification
6.7
-
about 60% of maximum activity. Biphasic loss of activity upon acidification
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
additional information
-
anthrax lethal toxin binds and enters murine neutrophils
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
89000
-
SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
-
1 * 90000, the protein is monomeric in solution, based on gel filtration
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
docking and molecular dynamics calculations to examine the anthrax lethal factor-MEK/MKK interaction along the catalytic channel up to a distance of 20 A from the zinc atom. The Zn-bound water molecule is predicted to form hydrogen bonds with the carbonyl oxygen of Ile, i.e. P1' of substrates MEK1, MKK3b, Leu, ie. P1' of substrate MKK4-1, and Leu, ie. P2 of substrate MKK6b as well as with the hydroxyl group of Thr, i.e. P2' of substrate MKK4-2. This hydrogen bond is an additional contact to the already existing polarization of the carbonyl oxygen between Zn and Glu687 carboxylate
-
in complex with inhibitor 3-(N-hydroxycarboxamido)-2-isobutylpropanoyl-Trp-methylamide, structure is used for pharmacopore model
-
in complex with inhibitors N-2-benzyl-N-2-[(4-fluoro-3-methylphenyl)sulfonyl]-N-hydroxy-D-alaninamide, N2-[(4-fluoro-3-methylphenyl)sulfonyl]-N-hydroxy-N-2-(4-nitrobenzyl)-D-alaninamide, N-2-[4-(aminomethyl)benzyl]-N-2-[(4-fluoro-3-methylphenyl)sulfonyl]-N-hydroxy-D-alaninamide to 2.2-2.5 A resolution. Identification of frequently populated conformational states termed bioactive, open and tight. The bioactive position is observed with large substrate peptides and leaves all peptide-recognition subsites open and accessible. The tight state is seen in unliganded and small-molecule complex structures. In this state, domain 3 is clamped over certain substrate subsites, blocking access. The open position appears to be an intermediate state between these extremes and is observed owing to steric constraints imposed by specific bound ligands
-
in complex with N terminus of MAPKK-2
-
structural analyzation by NMR-spectroscopy leading to 96% assignment of the backbone amides and overall assignment of 1HN, 15N, 13Calpha, 13Cbeta and 13C' chemical shifts to 85%
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5
-
increase in protein aggreagation between pH 4 and pH 5
733866
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, purified lethal toxin, at least 3 months, no loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
His-Trap HP nickel column chromatography, ammonium sulfate precipitation, and phenyl-Sepharose column chromatography
Ni-NTA agarose column chromatography
-
Q Sepharose column chromatography and Superdex 200 gel filtration
-
Superose 6 gel filtration
-
the recombinant LFn fusion proteins contain a vector-encoded His6 tag at the amino terminus and are purified by Ni2+-affinity chromatography to greater than 95% purity as determined by Coomassie staining
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Bacillus megaterium
-
expressed in Escherichia coli BL21 DE3 Star cells
expressed in Escherichia coli periplasm
-
expression in Bacillus megaterium
-
expression in Escherichia coli
-
expression of N-terminal domain, 233 residues, in Escherichia coli
-
fusion protein between lethal factor and the catalytic domain of diphtheria toxin is expressed in Escherichia coli BL21(DE3) cells
-
recombinant anthrax lethal toxin proteins consisting a model CD4 T-cell epitope from chicken ovalbumin (Ova) fused to nontoxic lethal factor (LFn). The antigen tags are generated by annealing single-stranded DNA oligonucleotides to form double-stranded DNA Plasmids are transformed into Escherichia coli BL21
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E678A
-
mutant fails to induce cell death
E678C
-
catalytically inactive
E687C
-
inactive
E687D
-
mutation in metal-binding site, decrease in catalytic activity
E720C
-
catalytic mutant
H686A
-
inactive
K518E/E682G
-
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
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
medicine
molecular biology
synthesis
-
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. The properties of the variants in blocking ion conductance through the protective antigen pore and translocating across planar phospholipid bilayers in response to a pH gradient are consistent with current concepts of the mechanism of polypeptide translocation through the pore. The semisynthesis platform allows for investigation of the interaction of the pore with its substrates