Journal ArticleDOI
A “Drug Sweeping” State of the TriABC Triclosan Efflux Pump from Pseudomonas aeruginosa
Lucien Fabre,Abigail T. Ntreh,Amira Yazidi,Inga V. Leus,Jon W. Weeks,Sudipta Bhattacharyya,Sudipta Bhattacharyya,Jakob Ruickoldt,Isabelle Rouiller,Isabelle Rouiller,Helen I. Zgurskaya,Jurgen Sygusch +11 more
TLDR
It is proposed that selective substrate translocation involves conformational gating at the tunnel narrowing that, together with conformational ordering of TriA and TriB, creates an engaged state capable of mediating substrate efflux.About:
This article is published in Structure.The article was published on 2021-03-04. It has received 7 citations till now. The article focuses on the topics: Membrane fusion protein & Periplasmic space.read more
Citations
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Journal ArticleDOI
Structure, Assembly, and Function of Tripartite Efflux and Type 1 Secretion Systems in Gram-Negative Bacteria
Ilyas Alav,Jessica Kobylka,Miriam S. Kuth,Klaas M. Pos,Martin Picard,Jessica M A Blair,Vassiliy N. Bavro +6 more
TL;DR: In this article, the authors summarize the recent advances in understanding of structural biology, function, and regulation of these systems, highlighting the previously undescribed role of periplasmic adaptor proteins (PAPs) in providing a common architectural scaffold across diverse families of transporters.
Journal ArticleDOI
Disinfectant resistance in bacteria: Mechanisms, spread, and resolution strategies.
TL;DR: In this article, a review focused on the resistance mechanisms of disinfectant resistant bacteria on biofilms, cell membrane permeability, efflux pumps, degradable enzymes, and disinfectant targets.
Journal ArticleDOI
Ever-Adapting RND Efflux Pumps in Gram-Negative Multidrug-Resistant Pathogens: A Race against Time.
Martijn Zwama,Kunihiko Nishino +1 more
TL;DR: In this article, the authors take a closer look at clinically, environmentally and laboratory-evolved Gram-negative bacterial strains and their decreased drug sensitivity as a result of mutations directly in the RND-type pumps themselves (from Escherichia coli, Salmonella-enterica, Neisseria gonorrhoeae, Pseudomonas aeruginosa, Acinetobacter baumannii and Legionella pneumophila).
Journal ArticleDOI
The Whole Is Bigger than the Sum of Its Parts: Drug Transport in the Context of Two Membranes with Active Efflux.
Valentin V. Rybenkov,Helen I. Zgurskaya,Chhandosee Ganguly,Inga V. Leus,Zhen Zhang,Mohammad Moniruzzaman +5 more
TL;DR: In this paper, the authors present a review of key experimental and computational approaches to the investigation of transport by individual translocators and in whole cells, summarizes key findings from these studies and outlines implications for antibiotic discovery.
Journal ArticleDOI
Multidrug Efflux Pumps and the Two-Faced Janus of Substrates and Inhibitors.
TL;DR: In this article, the authors discuss intriguing relationships between substrates and inhibitors of efflux pumps, as these two types of ligands face similar barriers and binding sites in the transporters and accessory proteins and both types of activities often occur with the same chemical scaffold.
References
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Journal ArticleDOI
Architecture and roles of periplasmic adaptor proteins in tripartite efflux assemblies
TL;DR: The understanding of the interaction between the OMFs and PAPs is the last piece remaining in the complete structure of the tripartite pump assembly puzzle, and targeting this interaction may provide a novel avenue for combating multidrug resistance.
Journal ArticleDOI
Transport of lipophilic carboxylates is mediated by transmembrane helix 2 in multidrug transporter AcrB.
TL;DR: It is proposed that fusidic acid and other lipophilic carboxylated drugs bound to the polyspecific substrate-binding module AcrB are actively displaced by an upward movement of TM2 towards theAcrB periplasmic porter domain in response to protonation events in the transmembrane domain.
Journal ArticleDOI
pH-induced Conformational Changes of AcrA, the Membrane Fusion Protein of Escherichia coli Multidrug Efflux System *
TL;DR: It is demonstrated that acidic pH induces oligomerization and conformational change of AcrA, and that the structural changes are reversible, suggesting that the mechanism of action of AcRA in drug efflux is similar to the viral membrane fusion proteins, and the efflux of substrates.
Journal ArticleDOI
Structures of intermediate transport states of ZneA, a Zn(II)/proton antiporter
John E. Pak,Elisabeth Ngonlong Ekendé,Efrem G. Kifle,Joseph D. O'Connell,Fabien De Angelis,Meseret B. Tessema,Kheiro-Mouna Derfoufi,Yaneth Robles-Colmenares,Rebecca A. Robbins,Erik Goormaghtigh,Guy Vandenbussche,Robert M. Stroud +11 more
TL;DR: Two X-ray crystal structures of a Zn(II) efflux pump, ZneA, that capture different intermediate states along the transport cycle are reported, providing mechanistic insights into the conformational changes required for substrate efflux by RND superfamily transporters.
Journal ArticleDOI
Constant pH Molecular Dynamics Reveals How Proton Release Drives the Conformational Transition of a Transmembrane Efflux Pump
TL;DR: Simulations offer dynamic details of how proton release drives the O-to-L transition in AcrB and address the controversy regarding the proton/drug stoichiometry, and further validates the membrane hybrid-solvent CpHMD technique for studies of proton-coupled transmembrane proteins which are currently poorly understood.