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

FEBS Lett. 2015 Dec 21;589(24 Pt B):3836-41. doi: 10.1016/j.febslet.2015.11.005. Epub 2015 Nov 11.


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.

Keywords: Anthrax; Conformational change; Lethal factor; Ligand-induced; Structure-based drug design; Zinc hydrolase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Bacterial / chemistry*
  • Antigens, Bacterial / metabolism*
  • Bacterial Toxins / antagonists & inhibitors
  • Bacterial Toxins / chemistry*
  • Bacterial Toxins / metabolism*
  • Binding Sites
  • Ligands
  • Matrix Metalloproteinase Inhibitors / chemistry
  • Matrix Metalloproteinase Inhibitors / metabolism*
  • Matrix Metalloproteinase Inhibitors / pharmacology*
  • Models, Molecular
  • Protein Conformation
  • Structure-Activity Relationship
  • Tyrosine / metabolism


  • Antigens, Bacterial
  • Bacterial Toxins
  • Ligands
  • Matrix Metalloproteinase Inhibitors
  • anthrax toxin
  • Tyrosine