Structural basis for the blockade of MATE multidrug efflux pumps

doi:10.1038/ncomms8995

Title: Structural basis for the blockade of MATE multidrug efflux pumps

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Authors:

Radchenko, Martha; Symersky, Jindrich; Nie, Rongxin; Lu, Min ^[1]

Rosalind

Publication Date:: Thu Jun 30 00:00:00 EDT 2016

Research Org.:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Org.:: UNIVERSITY

OSTI Identifier:: 1245872

Resource Type:: Journal Article

Resource Relation:: Journal Name: Nature Communications; Journal Volume: 6; Journal Issue: 7995

Country of Publication:: United States

Language:: ENGLISH

Citation Formats


                    Radchenko, Martha, Symersky, Jindrich, Nie, Rongxin, and Lu, Min. Structural basis for the blockade of MATE multidrug efflux pumps.  United States: N. p., 2016. 
        Web.  doi:10.1038/ncomms8995.

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                    Radchenko, Martha, Symersky, Jindrich, Nie, Rongxin, & Lu, Min. Structural basis for the blockade of MATE multidrug efflux pumps.  United States.  doi:10.1038/ncomms8995.

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                    Radchenko, Martha, Symersky, Jindrich, Nie, Rongxin, and Lu, Min. Thu .  
        "Structural basis for the blockade of MATE multidrug efflux pumps".  United States.  
        doi:10.1038/ncomms8995.

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@article{osti_1245872,

  title        = {Structural basis for the blockade of MATE multidrug efflux pumps},

  author       = {Radchenko, Martha and Symersky, Jindrich and Nie, Rongxin and Lu, Min},

  abstractNote = {},

  doi          = {10.1038/ncomms8995},

  journal      = {Nature Communications},

  number       = 7995,

  volume       = 6,

  place        = {United States},

  year         = {Thu Jun 30 00:00:00 EDT 2016},

  month        = {Thu Jun 30 00:00:00 EDT 2016}

}

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Journal Article:

DOI: 10.1038/ncomms8995

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Structural basis for the blockade of MATE multidrug efflux pumps

Radchenko, Martha ; Symersky, Jindrich ; Nie, Rongxin ; ... - Nature Communications

Multidrug and toxic compound extrusion (MATE) transporters underpin multidrug resistance by using the H ⁺ or Na ⁺ electrochemical gradient to extrude different drugs across cell membranes. MATE transporters can be further parsed into the DinF, NorM and eukaryotic subfamilies based on their amino-acid sequence similarity. Here we report the 3.0 Å resolution X-ray structures of a protonation-mimetic mutant of an H ⁺-coupled DinF transporter, as well as of an H ⁺-coupled DinF and a Na ⁺-coupled NorM transporters in complexes with verapamil, a small-molecule pharmaceutical that inhibits MATE-mediated multidrug extrusion. Combining structure-inspired mutational and functional studies, we confirm themore »« less
Cited by 17
DOI: 10.1038/ncomms8995

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Structural basis of multiple drug-binding capacity of the AcrB multidrug efflux pump.

Yu, Ew ; Mcdermott, Gerry ; Zgurskaya, H.I. ; ... - Science

No abstract prepared.
DOI: 10.1126/science.1083137
Structural insights into H[superscript +]-coupled multidrug extrusion by a MATE transporter

Lu, Min ; Radchenko, Martha ; Symersky, Jindrich ; ... - Nat. Struct. Mol. Biol.
DOI: 10.1038/nsmb.2687
Structures of a Na[superscript +]-coupled, substrate-bound MATE multidrug transporter

Lu, Min ; Symersky, Jindrich ; Radchenko, Martha ; ... - Proc. Natl. Acad. Sci. USA
DOI: 10.1073/pnas.1219901110
Reviving Antibiotics: Efflux Pump Inhibitors That Interact with AcrA, a Membrane Fusion Protein of the AcrAB-TolC Multidrug Efflux Pump

Abdali, Narges ; Parks, Jerry M. ; Haynes, Keith M. ; ... - ACS Infectious Diseases

Antibiotic resistance is a major threat to human welfare. Inhibitors of multidrug efflux pumps (EPIs) are promising alternative therapeutics that could revive activities of antibiotics and reduce bacterial virulence. Identification of new druggable sites for inhibition is critical for developing effective EPIs, especially in light of constantly emerging resistance. We describe new EPIs that interact with and possibly inhibit the function of periplasmic membrane fusion proteins, critical components of efflux pumps that are responsible for the activation of the transporter and the recruitment of the outer-membrane channel. The discovered EPIs bind to AcrA, a component of the prototypical AcrAB-TolC pump,more »« less
Cited by 3
DOI: 10.1021/acsinfecdis.6b00167

Full Text Available