General Information of the Protein
Protein ID
PT01240
Protein Name
Lethal factor
Secondarily
Protein Name
Anthrax lethal toxin endopeptidase component
Gene Name
LEF
Secondarily
Gene Name
pXO1-107
BXA0172
GBAA_pXO1_0172
Sequence
MNIKKEFIKVISMSCLVTAITLSGPVFIPLVQGAGGHGDVGMHVKEKEKNKDENKRKDEERNKTQEEHLKEIMKHIVKIEVKGEEAVKKEAAEKLLEKVPSDVLEMYKAIGGKIYIVDGDITKHISLEALSEDKKKIKDIYGKDALLHEHYVYAKEGYEPVLVIQSSEDYVENTEKALNVYYEIGKILSRDILSKINQPYQKFLDVLNTIKNASDSDGQDLLFTNQLKEHPTDFSVEFLEQNSNEVQEVFAKAFAYYIEPQHRDVLQLYAPEAFNYMDKFNEQEINLSLEELKDQRMLARYEKWEKIKQHYQHWSDSLSEEGRGLLKKLQIPIEPKKDDIIHSLSQEEKELLKRIQIDSSDFLSTEEKEFLKKLQIDIRDSLSEEEKELLNRIQVDSSNPLSEKEKEFLKKLKLDIQPYDINQRLQDTGGLIDSPSINLDVRKQYKRDIQNIDALLHQSIGSTLYNKIYLYENMNINNLTATLGADLVDSTDNTKINRGIFNEFKKNFKYSISSNYMIVDINERPALDNERLKWRIQLSPDTRAGYLENGKLILQRNIGLEIKDVQIIKQSEKEYIRIDAKVVPKSKIDTKIQEAQLNINQEWNKALGLPKYTKLITFNVHNRYASNIVESAYLILNEWKNNIQSDLIKKVTNYLVDGNGRFVFTDITLPNIAEQYTHQDEIYEQVHSKGLYVPESRSILLHGPSKGVELRNDSEGFIHEFGHAVDDYAGYLLDKNQSDLVTNSKKFIDIFKEEGSNLTSYGRTNEAEFFAEAFRLMHSTDHAERLKVQKNAPKTFQFINDQIKFIINS
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Organism
Bacillus anthracis
Protein Classification
Enzyme
>
Protease
>
Metallo protease
>
Metallo protease MAE clan
>
Metallo protease M34 family
Function
Lethal factor (LF), which constitutes one of the three proteins composing the anthrax toxin, is able to trigger rapid cell death in macrophages (PubMed:3711080, PubMed:8380282, PubMed:9563949, PubMed:10475971, PubMed:11104681, PubMed:9703991). Acts as a protease that cleaves the N-terminal of most dual specificity mitogen-activated protein kinase kinases (MAPKKs or MAP2Ks) (except for MAP2K5): cleavage invariably occurs within the N-terminal proline-rich region preceding the kinase domain, thus disrupting a sequence involved in directing specific protein-protein interactions necessary for the assembly of signaling complexes (PubMed:9563949, PubMed:10475971, PubMed:11104681, PubMed:9703991, PubMed:14718925). Also cleaves mouse Nlrp1b: host Nlrp1b cleavage promotes ubiquitination and degradation of the N-terminal part of Nlrp1b by the proteasome, thereby releasing the cleaved C-terminal part of Nlrp1b, which polymerizes and forms the Nlrp1b inflammasome followed by host cell pyroptosis (PubMed:10338520, PubMed:19651869, PubMed:31268597, PubMed:30872531). Able to cleave mouse Nlrp1b alleles 1 and 5, while it is not able to cleave Nlrp1b alleles 2, 3 and 4 (PubMed:16429160, PubMed:19651869). In contrast, does not cleave NLRP1 human ortholog (PubMed:19651869). LF is not toxic by itself and only acts as a lethal factor when associated with protective antigen (PA) to form the lethal toxin (LeTx): PA is required for LF translocation into the host cytosol (PubMed:9563949, PubMed:10475971, PubMed:11104681, PubMed:9703991).
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Uniprot ID
Primary ID:
P15917

Secondarily ID:
Q8KYJ6
Q933F6
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Subcellular Location
Secreted
Host cytoplasm
Host cytosol
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000014 , RAW 264.7
Compound ID Compound Name Compound Formula
CP0080616
4-[4-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)piperidine-1-carbonyl]benzenesulfonyl fluoride
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C18H18FN5O3S
 1
1
EC50 = 12 nM
   TI
   LI
   LO
   TS
CP0080614
4-[4-(4-aminopyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl]benzenesulfonyl fluoride
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C17H17FN6O3S
 1
1
EC50 = 23.7 nM
   TI
   LI
   LO
   TS
CP0369566
4-[4-(6-amino-2-methylpyrimidin-4-yl)oxypiperidine-1-carbonyl]benzenesulfonyl fluoride
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C17H19FN4O4S
 1
1
EC50 = 31.7 nM
   TI
   LI
   LO
   TS
CP0230263
4-[[4-(4-amino-6-methylpyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl]methyl]benzenesulfonyl fluoride
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C18H21FN6O2S
 1
1
EC50 = 60 nM
   TI
   LI
   LO
   TS
CP0369565
4-[4-(4-amino-6-methylpyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl]benzenesulfonyl fluoride
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C18H19FN6O3S
 1
1
EC50 = 104.6 nM
   TI
   LI
   LO
   TS
Clinical Information about the Protein
Target 1 ( Bacterial Lethal factor (Bact lef) )
Target Type Clinical trial Target
Disease 1 Target-related Disease  1
1 Corneal ulcer [ICD-11: 9A76]
Discontinued Drug(s) 1 Discontinued Drug  1
1 GM6001 Discontinued in Phase 2
Corneal ulcer