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

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: 11700563
DOI: 10.1038/n35101998

Experimental method

X-RAY DIFFRACTION (3.9 Å)