title: The metalloproteolytic activity of the anthrax lethal factor is substrate-inhibited.
abstract: The anthrax lethal factor (LF) is a Zn2+ endopeptidase specific for mitogen-activated protein kinase kinases (MAPKKs), which are cleaved within their N termini. Here, the proteolytic activity of LF has been investigated using novel chromogenic MAPKK-derived peptide substrates, which allowed us to determine the kinetic parameters of the reaction. LF displayed maximal proteolytic activity at the pH and temperature values of the cell cytosol, which is its site of action. LF undergoes substrate inhibition, in keeping with the non-productive binding geometry of the MAPPK-2 N terminus to LF.
authors.affiliation: Istituto di Neuroscienze, Consiglio Nazionale delle Ricerche, Via G. Colombo 3, 35121 Padova, Italy. fiorella.tonello@unipd.it
authors.forename: Fiorella
authors.initials: F
authors.lastname: Tonello
authors.forename: Paolo
authors.initials: P
authors.lastname: Ascenzi
authors.forename: Cesare
authors.initials: C
authors.lastname: Montecucco
mesh_terms: D000595:Amino Acid Sequence; D000942:Antigens, Bacterial; D001408:Bacillus anthracis / Q000472:pathogenicity; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D002863:Chromogenic Compounds; D006868:Hydrolysis; D066298:In Vitro Techniques; D007700:Kinetics; D045726:Metalloproteases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D013379:Substrate Specificity
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D002863:Chromogenic Compounds; D010446:Peptide Fragments; D011480:Protease Inhibitors; C030325:anthrax toxin; D020929:Mitogen-Activated Protein Kinase Kinases; D045726:Metalloproteases