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

Kimberly M. Maize; Elbek K. Kurbanov; Rodney L. Johnson; Elizabeth Ambrose Amin; Barry C. Finzel

doi:10.1016/j.febslet.2015.11.005

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

Kimberly M. Maize, Elbek K. Kurbanov, Rodney L. Johnson, Elizabeth Ambrose Amin, Barry C. Finzel

Medicinal Chemistry

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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.

Original language	English (US)
Pages (from-to)	3836-3841
Number of pages	6
Journal	FEBS Letters
Volume	589
Issue number	24
DOIs	https://doi.org/10.1016/j.febslet.2015.11.005
State	Published - Dec 21 2015

Bibliographical note

Publisher Copyright:
© 2015 Federation of European Biochemical Societies.

Keywords

Anthrax
Conformational change
Lethal factor
Ligand-induced
Structure-based drug design
Zinc hydrolase

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.febslet.2015.11.005

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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.",

keywords = "Anthrax, Conformational change, Lethal factor, Ligand-induced, Structure-based drug design, Zinc hydrolase",

author = "Maize, {Kimberly M.} and Kurbanov, {Elbek K.} and Johnson, {Rodney L.} and Amin, {Elizabeth Ambrose} and Finzel, {Barry C.}",

note = "Publisher Copyright: {\textcopyright} 2015 Federation of European Biochemical Societies.",

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doi = "10.1016/j.febslet.2015.11.005",

language = "English (US)",

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T1 - Ligand-induced expansion of the S1′ site in the anthrax toxin lethal factor

AU - Maize, Kimberly M.

AU - Kurbanov, Elbek K.

AU - Johnson, Rodney L.

AU - Amin, Elizabeth Ambrose

AU - Finzel, Barry C.

PY - 2015/12/21

Y1 - 2015/12/21

N2 - 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.

AB - 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.

KW - Anthrax

KW - Conformational change

KW - Lethal factor

KW - Ligand-induced

KW - Structure-based drug design

KW - Zinc hydrolase

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ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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