1J7N | Toxin | date | May 17, 2001 ![]() |
||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
title | Anthrax Toxin Lethal Factor | ||||||||||||||
authors | A.D.Pannifer, T.Y.Wong, R.Schwarzenbacher, M.Renatus, C.Petosa, R.J.Collier, J.Bienkowska, D.B.Lacy, S.Park, S.H.Leppla, P.Hanna R.C.Liddington | ||||||||||||||
compound | source | ||||||||||||||
Molecule: Lethal Factor Precursor Chain: A, B Synonym: Anthrax Toxin Lethal Factor Engineered: Yes |
Organism_scientific: Bacillus Anthracis Organism_common: Bacteria Gene: Lef Expression_system: Bacillus Anthracis Expression_system_common: Bacteria Expression_system_strain: Bh441 Expression_system_vector_type: Plasmid Expression_system_plasmid: Psj115 | ||||||||||||||
symmetry | Space Group: P 1 21 1 | R_factor | 0.229 | ||||||||||||
crystal cell |
| ||||||||||||||
method | X-Ray Diffraction | resolution | 2.30 Å | ||||||||||||
ligand | SO4, ZN | enzyme |
| ||||||||||||
domain | The pa-binding region is found in both b.anthracis ef and lf. Domain iv contains the catalytic center. It comprises four domains translocating component (pa); domains ii, iii and iv together create a long deep groove that holds the 16-residue n-terminal tail of mapkk before cleavage. | ||||||||||||||
similarity | Belongs to the peptidase m34 family.[ATLF] | ||||||||||||||
subunit | Anthrax toxins are composed of three distinct proteins, a protective antigen (pa), a lethal factor (lf) and an edema factor (ef). None of these is toxic by itself. Pa+lf forms the lethal toxin (letx); pa+ef forms the edema toxin (edtx). | ||||||||||||||
catalytic activ. | The only known protein substrates are mitogen-activated protein (map) kinase kinases. 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. | ||||||||||||||
induction | Positively transcriptionally regulated by atxa, which, in turn, is induced by bicarbonate and high temperatures (37 degrees celsius). | ||||||||||||||
subcellular loc. | Secreted protein. | ||||||||||||||
genes | BXA0172, GBAA, lef (B. anthracis) | ||||||||||||||
function | 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). One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. 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. Lf is the lethal factor that, when associated with pa, causes death. 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. | ||||||||||||||
Gene Ontology |
| ||||||||||||||
Primary reference | Crystal structure of the anthrax lethal factor., Pannifer AD, Wong TY, Schwarzenbacher R, Renatus M, Petosa C, Bienkowska J, Lacy DB, Collier RJ, Park S, Leppla SH, Hanna P, Liddington RC, Nature 2001 Nov 8;414(6860):229-33. PMID:11700563 |
Data retrieval |
![]() |
View 1J7N in 3D |
|
Visual 3D analysis of 1J7N |
|
Structure-derived information |
- Domain d1j7na3, region A:264-550 [Jmol] [rasmolscript] [script source] - Domain d1j7na1, region A:27-263 [Jmol] [rasmolscript] [script source] - Domain d1j7na2, region A:551-773 [Jmol] [rasmolscript] [script source] - Domain d1j7nb3, region B:264-550 [Jmol] [rasmolscript] [script source] - Domain d1j7nb1, region B:27-263 [Jmol] [rasmolscript] [script source] - Domain d1j7nb2, region B:551-776 [Jmol] [rasmolscript] [script source] |
Sequence-derived information |
Other resources with information on 1J7N |
Movements, Movies and Images |