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Ligand-induced expansion of the S1' site in the anthrax toxin lethal factor.

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.

SUBMITTER: Maize KM

PROVIDER: S-EPMC4688111 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Ligand-induced expansion of the S1' site in the anthrax toxin lethal factor.

Maize Kimberly M KM Kurbanov Elbek K EK Johnson Rodney L RL Amin Elizabeth Ambrose EA Finzel Barry C BC

FEBS letters 20151111 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 in ...[more]

PMID: 26578066

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Phage Display Analysis of Monoclonal Antibody Binding to Anthrax Toxin Lethal Factor

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Constitutive MEK1 activation rescues anthrax lethal toxin-induced vascular effects in vivo.

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| S-EPMC2981334 | biostudies-literature

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