A target-protection mechanism of antibiotic resistance at atomic resolution: insights into FusB-type fusidic acid resistance

Scientific Reports
Jennifer H TomlinsonAlex J O'Neill

Abstract

Antibiotic resistance in clinically important bacteria can be mediated by proteins that physically associate with the drug target and act to protect it from the inhibitory effects of an antibiotic. We present here the first detailed structural characterization of such a target protection mechanism mediated through a protein-protein interaction, revealing the architecture of the complex formed between the FusB fusidic acid resistance protein and the drug target (EF-G) it acts to protect. Binding of FusB to EF-G induces conformational and dynamic changes in the latter, shedding light on the molecular mechanism of fusidic acid resistance.

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Citations

Feb 8, 2018·Experimental Biology and Medicine·Nathan P CoussensDayle A Daines
Apr 19, 2017·FEMS Microbiology Reviews·Timothy J Foster
Jun 27, 2020·Nature Reviews. Microbiology·Daniel N WilsonAlex J O'Neill
Oct 2, 2020·Proceedings of the National Academy of Sciences of the United States of America·Jennifer H TomlinsonAntonio N Calabrese
Feb 26, 2019·Future Medicinal Chemistry·Ayesha Zainab Beg, Asad U Khan
Jun 3, 2021·International Journal of Molecular Sciences·Rya EroYong-Gui Gao
Jan 30, 2018·ACS Infectious Diseases·Liam K R Sharkey, Alex J O'Neill

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Methods Mentioned

BETA
X-ray
NMR

Software Mentioned

CHARMM27
PALES
NIH
NMRView
PyMOL Molecular Graphics System
NMRPipe
HADDOCK
Xplor
GROMACS

Related Concepts

Related Feeds

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

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