The anthrax lethal factor and its MAPK kinase-specific metalloprotease activity.
The anthrax lethal factor is a multi-domain protein toxin released by Bacillus anthracis which enters cells in a process mediated by the protective antigen and specific cell receptors. In the cytosol, the lethal factor cleaves the N-terminal tail of many MAPK kinases, thus deranging a major cell signaling pathway. The structural features at the basis of these activities of LF are reviewed here with particular attention to the proteolytic activity and to the identification of specific inhibitors. A significant similarity between the metalloprotease domain of the lethal factor and of that of the clostridial neurotoxins has been noted and is discussed.
Tonello
Fiorella
F
Dipartimento di Scienze Biomediche Sperimentali, Istituto CNR di Neuroscienze, Università di Padova, Viale G. Colombo 3, 35131 Padova, Italy.
Montecucco
Cesare
C
D000818:Animals; D000881:Anthrax / Q000201:enzymology / Q000382:microbiology; D000942:Antigens, Bacterial / Q000737:chemistry / Q000378:metabolism*; D001408:Bacillus anthracis / Q000201:enzymology* / Q000472:pathogenicity; D001427:Bacterial Toxins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D045726:Metalloproteases / Q000737:chemistry / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin; D020929:Mitogen-Activated Protein Kinase Kinases; D045726:Metalloproteases