Crystal structure of the anthrax lethal factor

摘要: Lethal factor (LF) is a protein (relative molecular mass 90,000) that critical in the pathogenesis of anthrax. It highly specific protease cleaves members mitogen-activated kinase (MAPKK) family near to their amino termini, leading inhibition one or more signalling pathways. Here we describe crystal structure LF and its complex with N terminus MAPKK-2. comprises four domains: domain I binds membrane-translocating component anthrax toxin, protective antigen (PA); domains II, III IV together create long deep groove holds 16-residue N-terminal tail MAPKK-2 before cleavage. Domain II resembles ADP-ribosylating toxin from Bacillus cereus, but active site has been mutated recruited augment substrate recognition. inserted into seems have arisen repeated duplication structural element II. distantly related zinc metalloprotease family, contains catalytic centre; it also I. The thus reveals evolved through process gene duplication, mutation fusion, an enzyme high unusual specificity.