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Ligand‐induced expansion of the S1′ site in the anthrax toxin lethal factor
Author(s) -
Maize Kimberly M.,
Kurbanov Elbek K.,
Johnson Rodney L.,
Amin Elizabeth Ambrose,
Finzel Barry C.
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.11.005
Subject(s) - bacillus anthracis , anthrax toxin , toxin , cytotoxicity , exotoxin , microbial toxins , ligand (biochemistry) , chemistry , enzyme , microbiology and biotechnology , biology , biochemistry , bacteria , in vitro , receptor , genetics , gene , recombinant dna , fusion protein
The Bacillus anthracis lethal factor (LF) is one component of a tripartite exotoxin partly responsible for persistent anthrax cytotoxicity after initial bacterial infection. Inhibitors of the zinc metalloproteinase have been investigated as potential therapeutic agents, but LF is a challenging target because inhibitors lack sufficient selectivity or possess poor pharmaceutical properties. These structural studies reveal an alternate conformation of the enzyme, induced upon binding of specific inhibitors, that opens a previously unobserved deep pocket termed S1′ ∗ which might afford new opportunities to design selective inhibitors that target this subsite.