1JKY
Crystal Structure of the Anthrax Lethal Factor (LF): Wild-type LF Complexed with the N-terminal Sequence of MAPKK2
Summary for 1JKY
Entry DOI | 10.2210/pdb1jky/pdb |
Related | 1J7N 1PWV 1PWW |
Descriptor | Lethal Factor, mitogen-activated protein kinase kinase 2 (2 entities in total) |
Functional Keywords | lethal toxin, mek2, mapkk, uncleaved substrate, protease-substrate complex, toxin |
Biological source | Bacillus anthracis More |
Cellular location | Secreted: P15917 |
Total number of polymer chains | 2 |
Total formula weight | 92150.06 |
Authors | Pannifer, A.D.,Wong, T.Y.,Schwarzenbacher, R.,Renatus, M.,Petosa, C.,Collier, R.J.,Bienkowska, J.,Lacy, D.B.,Park, S.,Leppla, S.H.,Hanna, P.,Liddington, R.C. (deposition date: 2001-07-13, release date: 2001-11-07, Last modification date: 2023-08-16) |
Primary citation | Pannifer, A.D.,Wong, T.Y.,Schwarzenbacher, R.,Renatus, M.,Petosa, C.,Bienkowska, J.,Lacy, D.B.,Collier, R.J.,Park, S.,Leppla, S.H.,Hanna, P.,Liddington, R.C. Crystal structure of the anthrax lethal factor. Nature, 414:229-233, 2001 Cited by PubMed Abstract: Lethal factor (LF) is a protein (relative molecular mass 90,000) that is critical in the pathogenesis of anthrax. It is a highly specific protease that cleaves members of the mitogen-activated protein kinase kinase (MAPKK) family near to their amino termini, leading to the inhibition of one or more signalling pathways. Here we describe the crystal structure of LF and its complex with the N terminus of MAPKK-2. LF comprises four domains: domain I binds the membrane-translocating component of anthrax toxin, the protective antigen (PA); domains II, III and IV together create a long deep groove that holds the 16-residue N-terminal tail of MAPKK-2 before cleavage. Domain II resembles the ADP-ribosylating toxin from Bacillus cereus, but the active site has been mutated and recruited to augment substrate recognition. Domain III is inserted into domain II, and seems to have arisen from a repeated duplication of a structural element of domain II. Domain IV is distantly related to the zinc metalloprotease family, and contains the catalytic centre; it also resembles domain I. The structure thus reveals a protein that has evolved through a process of gene duplication, mutation and fusion, into an enzyme with high and unusual specificity. PubMed: 11700563DOI: 10.1038/n35101998 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (3.9 Å) |
Structure validation
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