Stop the killer: how to inhibit the anthrax lethal factor metalloprotease.
Inhalation of anthrax spores rapidly develops into a deadly bacteraemia and toxaemia. Anthrax toxins include the lethal factor (LF), a mitogen-activated protein kinase (MAPK)-kinase-specific metalloprotease, which acts in the cell cytosol and plays a major part in anthrax pathogenesis. Recently, screening methods have led to the discovery of LF inhibitors that are membrane permeable. This will pave the way for design of novel anthrax therapeutics that are capable of inhibiting the metalloprotease activity of LF in vivo.
Montecucco
Cesare
C
Istituto Veneto di Medicina Molecolare, Via Orus, 35121 Padua, Italy. cesare.montecucco@unipd.it
Tonello
Fiorella
F
Zanotti
Giuseppe
G
D000881:Anthrax / Q000201:enzymology*; D000942:Antigens, Bacterial; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D045726:Metalloproteases / Q000037:antagonists & inhibitors*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D010455:Peptides / Q000494:pharmacology*
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004791:Enzyme Inhibitors; D010455:Peptides; C030325:anthrax toxin; D020929:Mitogen-Activated Protein Kinase Kinases; D045726:Metalloproteases