Target Information
Target General Infomation | |||||
---|---|---|---|---|---|
Target ID |
T72335
|
||||
Former ID |
TTDR01027
|
||||
Target Name |
Lethal factor
|
||||
Gene Name |
lef
|
||||
Synonyms |
ALF; Anthrax lethal factor; Anthrax lethal toxin endopeptidase component; LF; lef
|
||||
Target Type |
Clinical Trial
|
||||
Disease | Bacillus anthracis infection [ICD10: A22] | ||||
Function |
One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. LF is the lethal factor that, when associated with PA, causes death. LF is not toxic by itself. It is 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. There may be other cytosolic targets of LF involved in cytotoxicity. The proteasome may mediate a toxic process initiated by LF in the cell cytosol involving degradation of unidentified molecules that are essential for macrophage homeostasis. This is an early step in LeTx intoxication, but it is downstream of the cleavage by LF of MEK1 or other putative substrates.
|
||||
BioChemical Class |
Peptidase
|
||||
Target Validation |
T72335
|
||||
UniProt ID | |||||
EC Number |
EC 3.4.24.83
|
||||
Sequence |
MNIKKEFIKVISMSCLVTAITLSGPVFIPLVQGAGGHGDVGMHVKEKEKNKDENKRKDEE
RNKTQEEHLKEIMKHIVKIEVKGEEAVKKEAAEKLLEKVPSDVLEMYKAIGGKIYIVDGD ITKHISLEALSEDKKKIKDIYGKDALLHEHYVYAKEGYEPVLVIQSSEDYVENTEKALNV YYEIGKILSRDILSKINQPYQKFLDVLNTIKNASDSDGQDLLFTNQLKEHPTDFSVEFLE QNSNEVQEVFAKAFAYYIEPQHRDVLQLYAPEAFNYMDKFNEQEINLSLEELKDQRMLAR YEKWEKIKQHYQHWSDSLSEEGRGLLKKLQIPIEPKKDDIIHSLSQEEKELLKRIQIDSS DFLSTEEKEFLKKLQIDIRDSLSEEEKELLNRIQVDSSNPLSEKEKEFLKKLKLDIQPYD INQRLQDTGGLIDSPSINLDVRKQYKRDIQNIDALLHQSIGSTLYNKIYLYENMNINNLT ATLGADLVDSTDNTKINRGIFNEFKKNFKYSISSNYMIVDINERPALDNERLKWRIQLSP DTRAGYLENGKLILQRNIGLEIKDVQIIKQSEKEYIRIDAKVVPKSKIDTKIQEAQLNIN QEWNKALGLPKYTKLITFNVHNRYASNIVESAYLILNEWKNNIQSDLIKKVTNYLVDGNG RFVFTDITLPNIAEQYTHQDEIYEQVHSKGLYVPESRSILLHGPSKGVELRNDSEGFIHE FGHAVDDYAGYLLDKNQSDLVTNSKKFIDIFKEEGSNLTSYGRTNEAEFFAEAFRLMHST DHAERLKVQKNAPKTFQFINDQIKFIINS |
||||
Drugs and Mode of Action | |||||
Inhibitor | 3-(2,5-dimethyl-1H-pyrrol-1-yl)benzoic acid | Drug Info | [528374] | ||
GF-109203 | Drug Info | [528823] | |||
GM6001 | Drug Info | [551393] | |||
GNF-PF-600 | Drug Info | [527949] | |||
MMI270 | Drug Info | [527922] | |||
N,N'-Bis(4-Amino-2-Methylquinolin-6-Yl)Urea | Drug Info | [551393] | |||
N,N-Dimethylsphingosine | Drug Info | [528823] | |||
N-(3,4,5-trihydroxyphenethyl)oleamide | Drug Info | [528901] | |||
N-(3,4-dihydroxybenzyl)oleamide | Drug Info | [529351] | |||
N-(Sulfanylacetyl)Tyrosylprolylmethioninamide | Drug Info | [551393] | |||
N-hydroxy-4-(2-oleamidoethyl)benzamide | Drug Info | [528901] | |||
N-hydroxy-4-(oleamidomethyl)benzamide | Drug Info | [529351] | |||
N-oleoyl-dopamine | Drug Info | [528901] | |||
NSC-622445 | Drug Info | [528374] | |||
Modulator | IQ-DAA | Drug Info | |||
Pathways | |||||
Pathway Interaction Database | Cellular roles of Anthrax toxin | ||||
Reactome | Uptake and function of anthrax toxins | ||||
References | |||||
Ref 527922 | Bioorg Med Chem Lett. 2006 Feb 15;16(4):964-8. Epub 2005 Dec 9.The discovery of a potent and selective lethal factor inhibitor for adjunct therapy of anthrax infection. | ||||
Ref 527949 | J Med Chem. 2006 Jan 12;49(1):27-30.Anthrax lethal factor protease inhibitors: synthesis, SAR, and structure-based 3D QSAR studies. | ||||
Ref 528374 | J Med Chem. 2006 Aug 24;49(17):5232-44.Novel small-molecule inhibitors of anthrax lethal factor identified by high-throughput screening. | ||||
Ref 528823 | Antimicrob Agents Chemother. 2007 Jul;51(7):2403-11. Epub 2007 May 7.Amiodarone and bepridil inhibit anthrax toxin entry into host cells. | ||||
Ref 528901 | Bioorg Med Chem Lett. 2007 Aug 15;17(16):4575-8. Epub 2007 Jun 6.Inhibitors of anthrax lethal factor. |
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.