Titratable residues that drive RND efflux: insights from molecular simulations
Titratable residues that drive RND efflux: insights from molecular simulations
The resistance–nodulation–division efflux machinery confers antimicrobial resistance to Gram-negative bacteria by actively pumping antibiotics out of the cell. The protein complex is powered by proton motive force; however, the proton transfer mechanism itself and indeed even its stoichiometry is still unclear. Here we review computational studies from the last decade that focus on elucidating the number of protons transferred per conformational cycle of the pump. Given the difficulties in studying proton movement using even state-of-the-art structural biology methods, the contributions from computational studies have been invaluable from a mechanistic perspective.
antimicrobial resistance, conformational cycling, efflux, molecular dynamics, protonation states
Clark, Robert
eceef374-6a98-4e6f-be55-75ae473f32f9
Newman, Kahlan E.
7fccd66d-2aa1-4dd6-b477-2ad528389f83
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394
1 April 2024
Clark, Robert
eceef374-6a98-4e6f-be55-75ae473f32f9
Newman, Kahlan E.
7fccd66d-2aa1-4dd6-b477-2ad528389f83
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394
Clark, Robert, Newman, Kahlan E. and Khalid, Syma
(2024)
Titratable residues that drive RND efflux: insights from molecular simulations.
QRB Discovery, 5 (5), [e5].
(doi:10.1017/qrd.2024.6).
Abstract
The resistance–nodulation–division efflux machinery confers antimicrobial resistance to Gram-negative bacteria by actively pumping antibiotics out of the cell. The protein complex is powered by proton motive force; however, the proton transfer mechanism itself and indeed even its stoichiometry is still unclear. Here we review computational studies from the last decade that focus on elucidating the number of protons transferred per conformational cycle of the pump. Given the difficulties in studying proton movement using even state-of-the-art structural biology methods, the contributions from computational studies have been invaluable from a mechanistic perspective.
Text
titratable-residues-that-drive-rnd-efflux-insights-from-molecular-simulations
- Version of Record
More information
Accepted/In Press date: 7 March 2024
Published date: 1 April 2024
Keywords:
antimicrobial resistance, conformational cycling, efflux, molecular dynamics, protonation states
Identifiers
Local EPrints ID: 493579
URI: http://eprints.soton.ac.uk/id/eprint/493579
ISSN: 2633-2892
PURE UUID: e8f12efc-21af-4bcb-9a9e-7c7c23dff72a
Catalogue record
Date deposited: 06 Sep 2024 16:48
Last modified: 06 Sep 2024 17:14
Export record
Altmetrics
Contributors
Author:
Robert Clark
Author:
Kahlan E. Newman
Author:
Syma Khalid
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics