Ligand-induced expansion of the S1' site in the anthrax toxin lethal factor
Kimberly M Maize1, Elbek K Kurbanov1, Rodney L Johnson1
1Department of Medicinal Chemistry, University of Minnesota, 308 Harvard St SE, 8-101 Weaver-Densford Hall, Minneapolis, MN 55455, United States.
Abstract:
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.
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