title: 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.
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, 308 Harvard St SE, 8-101 Weaver-Densford Hall, Minneapolis, MN 55455, United States.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Maize
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, 308 Harvard St SE, 8-101 Weaver-Densford Hall, Minneapolis, MN 55455, United States.
authors.forename: Elbek K
authors.initials: EK
authors.lastname: Kurbanov
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, 308 Harvard St SE, 8-101 Weaver-Densford Hall, Minneapolis, MN 55455, United States.
authors.forename: Rodney L
authors.initials: RL
authors.lastname: Johnson
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, 308 Harvard St SE, 8-101 Weaver-Densford Hall, Minneapolis, MN 55455, United States.
authors.forename: Elizabeth Ambrose
authors.initials: EA
authors.lastname: Amin
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, 308 Harvard St SE, 8-101 Weaver-Densford Hall, Minneapolis, MN 55455, United States. Electronic address: finze007@umn.edu.
authors.forename: Barry C
authors.initials: BC
authors.lastname: Finzel
mesh_terms: D000942:Antigens, Bacterial / Q000737:chemistry* / Q000378:metabolism*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D008024:Ligands; D061965:Matrix Metalloproteinase Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D008958:Models, Molecular; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D008024:Ligands; D061965:Matrix Metalloproteinase Inhibitors; C030325:anthrax toxin; D014443:Tyrosine
keywords: Anthrax; Conformational change; Lethal factor; Ligand-induced; Structure-based drug design; Zinc hydrolase