| 1JKY |
Toxin |
date |
Jul 13, 2001  |
|---|
| title | Crystal Structure Of The Anthrax Lethal Factor (Lf): Wild- Type Lf Complexed With The N-Terminal Sequence Of Mapkk2 |
| 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
Chain: A
Synonym: Lf
Engineered: Yes
Other_details: Mature Form
|
Organism_scientific: Bacillus Anthracis
Organism_common: Bacteria
Expression_system: Bacillus Anthracis
Expression_system_common: Bacteria
Expression_system_strain: Bh441
|
Molecule: Mitogen-Activated Protein Kinase Kinase 2
Chain: B
Fragment: N-Terminus
Synonym: Mapkk2, Mek2
Ec: 2.7.1.-
Engineered: Yes
|
Synthetic: Yes
Other_details: This Protein Was Chemically Synthesized. It Is Based On A Sequence From Homo Sapiens (Human).
|
| symmetry | Space Group: I 41 3 2
| R_factor | 0.296 |
crystal
cell |
| length a |
length b |
length c |
angle alpha |
angle beta |
angle gamma |
| 330.700 |
330.700 |
330.700 |
90.00 |
90.00 |
90.00 |
|
| method | X-Ray Diffraction | resolution | 3.90 Å |
| ligand |
| enzyme | Transferase
E.C.2.7.1
BRENDA
|
| note | 1JKY (Molecule of the Month:pdb28) |
| 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 |
