NDLI: Antiinfectives targeting enzymes and the proton motive force

Content Provider	PubMed Central
Author	Feng, Xinxin Zhu, Wei Schurig-briccio, Lici A. Lindert, Steffen Shoen, Carolyn Hitchings, Reese Li, Jikun Wang, Yang Baig, Noman Zhou, Tianhui Kim, Boo Kyung Crick, Dean C. Cynamon, Michael Mccammon, J. Andrew Gennis, Robert B. Oldfield, Eric
Abstract	Uncoupling agents might be expected to be generally cytotoxic, but many US Food and Drug Administration (FDA)-approved drugs do have activity as uncouplers, in addition to targeting enzymes. There is therefore interest in the discovery of antibiotics that have such multitarget activity. Here, we show that some FDA-approved drugs, such as clofazimine, clomiphene, and bedaquiline, with antiinfective activity act as uncouplers. Using molecular dynamics-based in silico screening, we also discovered that the brain cancer drug lead vacquinol is an uncoupler that inhibits an enzyme involved in the formation of tuberculosis (TB) virulence factors, in addition to killing TB bacteria. Our results indicate strong drug–membrane interactions, and that screening for combined enzyme inhibition plus uncoupler activity will lead to new antibiotic leads.
Related Links	http://dx.doi.org/10.1073/pnas.1521988112
Starting Page	7073
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	51
Volume Number	112
Language	English
Publisher	National Academy of Sciences
Publisher Date	2015-12-01
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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Antiinfectives targeting enzymes and the proton motive force.

Proton motive force may regulate cell wall-associated enzymes of Bacillus subtilis.

Membrane protein insertion and proton-motive-force-dependent secretion through the bacterial holo-translocon SecYEG–SecDF–YajC–YidC

In situ measurement of the electrical potential across the phagosomal membrane using FRET and its contribution to the proton-motive force

Transport of amino acids in Lactobacillus casei by proton-motive-force-dependent and non-proton-motive-force-dependent mechanisms.

Myxobacteria gliding motility requires cytoskeleton rotation powered by proton motive force

Proton-motive force stimulates the proteolytic activity of FtsH, a membrane-bound ATP- dependent protease in Escherichia coli

In situ measurement of the electrical potential across the phagosomal membrane using FRET and its contribution to the proton-motive force.

Myxobacteria gliding motility requires cytoskeleton rotation powered by proton motive force.

Antiinfectives targeting enzymes and the proton motive force

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Antiinfectives targeting enzymes and the proton motive force.

Proton motive force may regulate cell wall-associated enzymes of Bacillus subtilis.

Membrane protein insertion and proton-motive-force-dependent secretion through the bacterial holo-translocon SecYEG–SecDF–YajC–YidC

In situ measurement of the electrical potential across the phagosomal membrane using FRET and its contribution to the proton-motive force

Transport of amino acids in Lactobacillus casei by proton-motive-force-dependent and non-proton-motive-force-dependent mechanisms.

Myxobacteria gliding motility requires cytoskeleton rotation powered by proton motive force

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Myxobacteria gliding motility requires cytoskeleton rotation powered by proton motive force.

Antiinfectives targeting enzymes and the proton motive force