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. Furthermore, 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:
-
- Univ. of Minnesota, Minneapolis, MN (United States)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- National Institutes of Health (NIH)
- OSTI Identifier:
- 1237749
- Grant/Contract Number:
- R01 AI083234
- Resource Type:
- Accepted Manuscript
- Journal Name:
- FEBS Letters
- Additional Journal Information:
- Journal Volume: 589; Journal Issue: 24PartB; Journal ID: ISSN 0014-5793
- Publisher:
- Federation of European Biochemical Societies
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; LF; lethal factor; EF; edema factor; PA; protective antigen; MMP; matrix metalloprotease; Anthrax; Ligand-induced; Conformational change; Structure-based drug design; Zinc hydrolase
Citation Formats
Maize, Kimberly M., Kurbanov, Elbek K., Johnson, Rodney L., Amin, Elizabeth Ambrose, and Finzel, Barry C. Ligand-induced expansion of the S1' site in the anthrax toxin lethal factor. United States: N. p., 2015.
Web. doi:10.1016/j.febslet.2015.11.005.
Maize, Kimberly M., Kurbanov, Elbek K., Johnson, Rodney L., Amin, Elizabeth Ambrose, & Finzel, Barry C. Ligand-induced expansion of the S1' site in the anthrax toxin lethal factor. United States. https://doi.org/10.1016/j.febslet.2015.11.005
Maize, Kimberly M., Kurbanov, Elbek K., Johnson, Rodney L., Amin, Elizabeth Ambrose, and Finzel, Barry C. Wed .
"Ligand-induced expansion of the S1' site in the anthrax toxin lethal factor". United States. https://doi.org/10.1016/j.febslet.2015.11.005. https://www.osti.gov/servlets/purl/1237749.
@article{osti_1237749,
title = {Ligand-induced expansion of the S1' site in the anthrax toxin lethal factor},
author = {Maize, Kimberly M. and Kurbanov, Elbek K. and Johnson, Rodney L. and Amin, Elizabeth Ambrose and Finzel, Barry C.},
abstractNote = {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. Furthermore, 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.},
doi = {10.1016/j.febslet.2015.11.005},
journal = {FEBS Letters},
number = 24PartB,
volume = 589,
place = {United States},
year = {Wed Nov 11 00:00:00 EST 2015},
month = {Wed Nov 11 00:00:00 EST 2015}
}
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