biostudies-literatureMaize KMUniversity of Minnesota College of PharmacyNIAID NIH HHSAmerican Foundation for Pharmaceutical Education Pre-Doctoral FellowshipNational Institutes of HealthUniversity of Minnesota Doctoral Dissertation FellowshipUniversity of Minnesota Office of the Vice President for Research3836-41https://www.ebi.ac.uk/biostudies/studies/S-EPMC4688111biostudies-literatureUnknown589(24 Pt B)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.FEBS lettersLigand-induced expansion of the S1' site in the anthrax toxin lethal factor.PMC4688111R01 AI083234Amin EAFinzel BCKurbanov EKJohnson RLMaize KMfalseLigand-induced expansion of the S1' site in the anthrax toxin lethal factor.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.2015-01-01T00:00:00Z2015 Dec2024-10-16T08:06:46.101Z2019-03-27T02:05:38ZS-EPMC46881112657806610.1016/j.febslet.2015.11.005