Dynamics of Intact MexAB-OprM Efflux Pump: Focusing on the MexA-OprM Interface
Abstract
Antibiotic efflux is one of the most critical mechanisms leading to bacterial multidrug resistance. Antibiotics are effluxed out of the bacterial cell by a tripartite efflux pump, a complex machinery comprised of outer membrane, periplasmic adaptor, and inner membrane protein components. Understanding the mechanism of efflux pump assembly and its dynamics could facilitate discovery of novel approaches to counteract antibiotic resistance in bacteria. We built here an intact atomistic model of the Pseudomonas aeruginosa MexAB-OprM pump in a Gram-negative membrane model that contained both inner and outer membranes separated by a periplasmic space. All-atom molecular dynamics (MD) simulations confirm that the fully assembled pump is stable in the microsecond timescale. Using a combination of all-atom and coarse-grained MD simulations and sequence covariation analysis, we characterized the interface between MexA and OprM in the context of the entire efflux pump. These analyses suggest a plausible mechanism by which OprM is activated via opening of its periplasmic aperture through a concerted interaction with MexA.
- Authors:
-
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- Goethe Univ., Frankfurt (Germany). Inst. of Biochemistry. Cluster of Excellence Frankfurt
- Univ. of Oklahoma, Norman, OK (United States). Dept. of Chemistry and Biochemistry
- Publication Date:
- Research Org.:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States); Univ. of Oklahoma, Norman, OK (United States); Goethe Univ., Frankfurt (Germany)
- Sponsoring Org.:
- USDOE; LANL Laboratory Directed Research and Development (LDRD) Program; Defense Threat Reduction Agency (DTRA) (United States); National Inst. of Health (NIH) (United States); German Research Foundation (DFG); Human Frontier Science Program (HFSP)
- OSTI Identifier:
- 1440470
- Report Number(s):
- LA-UR-16-27246
Journal ID: ISSN 2045-2322
- Grant/Contract Number:
- AC52-06NA25396; HDTRA1-14-1-0019; AI052293; SFB807; EXC115; HFSP-RGP0034/2013
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Scientific Reports
- Additional Journal Information:
- Journal Volume: 7; Journal ID: ISSN 2045-2322
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES
Citation Formats
Lopez, Cesar A., Travers, Timothy, Pos, Klaas M., Zgurskaya, Helen I., and Gnanakaran, S. Dynamics of Intact MexAB-OprM Efflux Pump: Focusing on the MexA-OprM Interface. United States: N. p., 2017.
Web. doi:10.1038/s41598-017-16497-w.
Lopez, Cesar A., Travers, Timothy, Pos, Klaas M., Zgurskaya, Helen I., & Gnanakaran, S. Dynamics of Intact MexAB-OprM Efflux Pump: Focusing on the MexA-OprM Interface. United States. https://doi.org/10.1038/s41598-017-16497-w
Lopez, Cesar A., Travers, Timothy, Pos, Klaas M., Zgurskaya, Helen I., and Gnanakaran, S. Tue .
"Dynamics of Intact MexAB-OprM Efflux Pump: Focusing on the MexA-OprM Interface". United States. https://doi.org/10.1038/s41598-017-16497-w. https://www.osti.gov/servlets/purl/1440470.
@article{osti_1440470,
title = {Dynamics of Intact MexAB-OprM Efflux Pump: Focusing on the MexA-OprM Interface},
author = {Lopez, Cesar A. and Travers, Timothy and Pos, Klaas M. and Zgurskaya, Helen I. and Gnanakaran, S.},
abstractNote = {Antibiotic efflux is one of the most critical mechanisms leading to bacterial multidrug resistance. Antibiotics are effluxed out of the bacterial cell by a tripartite efflux pump, a complex machinery comprised of outer membrane, periplasmic adaptor, and inner membrane protein components. Understanding the mechanism of efflux pump assembly and its dynamics could facilitate discovery of novel approaches to counteract antibiotic resistance in bacteria. We built here an intact atomistic model of the Pseudomonas aeruginosa MexAB-OprM pump in a Gram-negative membrane model that contained both inner and outer membranes separated by a periplasmic space. All-atom molecular dynamics (MD) simulations confirm that the fully assembled pump is stable in the microsecond timescale. Using a combination of all-atom and coarse-grained MD simulations and sequence covariation analysis, we characterized the interface between MexA and OprM in the context of the entire efflux pump. These analyses suggest a plausible mechanism by which OprM is activated via opening of its periplasmic aperture through a concerted interaction with MexA.},
doi = {10.1038/s41598-017-16497-w},
journal = {Scientific Reports},
number = ,
volume = 7,
place = {United States},
year = {Tue Nov 28 00:00:00 EST 2017},
month = {Tue Nov 28 00:00:00 EST 2017}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 20 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Nonphysical sampling distributions in Monte Carlo free-energy estimation: Umbrella sampling
journal, February 1977
- Torrie, G. M.; Valleau, J. P.
- Journal of Computational Physics, Vol. 23, Issue 2
Assembly and Channel Opening in a Bacterial Drug Efflux Machine
journal, April 2008
- Bavro, Vassiliy N.; Pietras, Zbigniew; Furnham, Nicholas
- Molecular Cell, Vol. 30, Issue 1, p. 114-121
Structure of the AcrAB–TolC multidrug efflux pump
journal, April 2014
- Du, Dijun; Wang, Zhao; James, Nathan R.
- Nature, Vol. 509, Issue 7501
Tripartite assembly of RND multidrug efflux pumps
journal, February 2016
- Daury, Laetitia; Orange, François; Taveau, Jean-Christophe
- Nature Communications, Vol. 7, Issue 1
Resistance Mechanisms in Pseudomonas aeruginosa and Other Nonfermentative Gram‐Negative Bacteria
journal, August 1998
- Hancock, Robert E. W.
- Clinical Infectious Diseases, Vol. 27, Issue s1
Antibiotic efflux mechanisms
journal, January 1999
- Nikaido, Hiroshi; Zgurskaya, Helen I.
- Current Opinion in Infectious Diseases, Vol. 12, Issue 6
The effects of active efflux pumps on antibiotic resistance in Pseudomonas aeruginosa
journal, June 2014
- Terzi, Huseyin Agah; Kulah, Canan; Ciftci, İhsan Hakkı
- World Journal of Microbiology and Biotechnology, Vol. 30, Issue 10
Permeability of Pseudomonas aeruginosa outer membrane to hydrophilic solutes
journal, November 1982
- Yoshimura, F.; Nikaido, H.
- Journal of Bacteriology, Vol. 152, Issue 2
Comparison of simple potential functions for simulating liquid water
journal, July 1983
- Jorgensen, William L.; Chandrasekhar, Jayaraman; Madura, Jeffry D.
- The Journal of Chemical Physics, Vol. 79, Issue 2
Decreased outer membrane permeability in imipenem-resistant mutants of Pseudomonas aeruginosa.
journal, August 1989
- Trias, J.; Dufresne, J.; Levesque, R. C.
- Antimicrobial Agents and Chemotherapy, Vol. 33, Issue 8
Breaking the Spell: Combating Multidrug Resistant ‘Superbugs’
journal, February 2016
- Khan, Shahper N.; Khan, Asad U.
- Frontiers in Microbiology, Vol. 7
Molecular dynamics flexible fitting: A practical guide to combine cryo-electron microscopy and X-ray crystallography
journal, October 2009
- Trabuco, Leonardo G.; Villa, Elizabeth; Schreiner, Eduard
- Methods, Vol. 49, Issue 2
Flexibility in a Drug Transport Accessory Protein: Molecular Dynamics Simulations of MexA
journal, July 2006
- Vaccaro, Loredana; Koronakis, Vassilis; Sansom, Mark S. P.
- Biophysical Journal, Vol. 91, Issue 2
Multidrug efflux transporter, AcrB—the pumping mechanism
journal, August 2008
- Murakami, S.
- Current Opinion in Structural Biology, Vol. 18, Issue 4
Bacterial Multidrug Efflux Transporters
journal, May 2014
- Delmar, Jared A.; Su, Chih-Chia; Yu, Edward W.
- Annual Review of Biophysics, Vol. 43, Issue 1
Crystal structure of bacterial multidrug efflux transporter AcrB
journal, October 2002
- Murakami, Satoshi; Nakashima, Ryosuke; Yamashita, Eiki
- Nature, Vol. 419, Issue 6907
Multiple conformational states and gate opening of outer membrane protein TolC revealed by molecular dynamics simulations: MD Simulation of TolC
journal, June 2014
- Wang, Beibei; Weng, Jingwei; Wang, Wenning
- Proteins: Structure, Function, and Bioinformatics, Vol. 82, Issue 9
Keep It Flexible: Driving Macromolecular Rotary Motions in Atomistic Simulations with GROMACS
journal, March 2011
- Kutzner, Carsten; Czub, Jacek; Grubmüller, Helmut
- Journal of Chemical Theory and Computation, Vol. 7, Issue 5
Isolation and characterization of antibiotic-resistant bacteria from pharmaceutical industrial wastewaters
journal, December 2015
- Tahrani, Leyla; Soufi, Leila; Mehri, Ines
- Microbial Pathogenesis, Vol. 89
Lipid14: The Amber Lipid Force Field
journal, January 2014
- Dickson, Callum J.; Madej, Benjamin D.; Skjevik, Åge A.
- Journal of Chemical Theory and Computation, Vol. 10, Issue 2
Crystal Structure of the Periplasmic Component of a Tripartite Macrolide-Specific Efflux Pump
journal, April 2009
- Yum, Soohwan; Xu, Yongbin; Piao, Shunfu
- Journal of Molecular Biology, Vol. 387, Issue 5
Structure of the periplasmic component of a bacterial drug efflux pump
journal, June 2004
- Higgins, M. K.; Bokma, E.; Koronakis, E.
- Proceedings of the National Academy of Sciences, Vol. 101, Issue 27
Structure of the MacAB–TolC ABC-type tripartite multidrug efflux pump
journal, May 2017
- Fitzpatrick, Anthony W. P.; Llabrés, Salomé; Neuberger, Arthur
- Nature Microbiology, Vol. 2, Issue 7
Keep it Flexible: Driving Macromolecular Rotary Motions in Atomistic Simulations with Gromacs
journal, January 2012
- Kutzner, Carsten; Czub, Jacek; Grubmueller, Helmut
- Biophysical Journal, Vol. 102, Issue 3
Multidrug efflux pumps in Gram-negative bacteria and their role in antibiotic resistance
journal, October 2014
- Blair, Jessica MA; Richmond, Grace E.; Piddock, Laura JV
- Future Microbiology, Vol. 9, Issue 10
Interactions underlying assembly of the Escherichia coli AcrAB-TolC multidrug efflux system: Multidrug efflux system assembly
journal, June 2004
- Touzé, Thierry; Eswaran, Jeyanthy; Bokma, Evert
- Molecular Microbiology, Vol. 53, Issue 2
LAMBADA and InflateGRO2: Efficient Membrane Alignment and Insertion of Membrane Proteins for Molecular Dynamics Simulations
journal, September 2012
- Schmidt, Thomas H.; Kandt, Christian
- Journal of Chemical Information and Modeling, Vol. 52, Issue 10
Structural basis of RND-type multidrug exporters
journal, April 2015
- Yamaguchi, Akihito; Nakashima, Ryosuke; Sakurai, Keisuke
- Frontiers in Microbiology, Vol. 6
Structural and Dynamical Insights into the Opening Mechanism of P. aeruginosa OprM Channel
journal, March 2010
- Phan, Gilles; Benabdelhak, Houssain; Lascombe, Marie-Bernard
- Structure, Vol. 18, Issue 4
Computational Methodologies for Real-Space Structural Refinement of Large Macromolecular Complexes
journal, July 2016
- Goh, Boon Chong; Hadden, Jodi A.; Bernardi, Rafael C.
- Annual Review of Biophysics, Vol. 45, Issue 1
Mutations in MexB that affect the efflux of antibiotics with cytoplasmic targets
journal, May 2012
- Ohene-Agyei, Thelma; Lea, Jon D.; Venter, Henrietta
- FEMS Microbiology Letters, Vol. 333, Issue 1
An allosteric transport mechanism for the AcrAB-TolC multidrug efflux pump
journal, March 2017
- Wang, Zhao; Fan, Guizhen; Hryc, Corey F.
- eLife, Vol. 6
The assembly and disassembly of the AcrAB-TolC three-component multidrug efflux pump
journal, September 2015
- Müller, Reinke Tobias; Pos, Klaas Martinus
- Biological Chemistry, Vol. 396, Issue 9-10
Functional Rotation Induced by Alternating Protonation States in the Multidrug Transporter AcrB: All-Atom Molecular Dynamics Simulations
journal, October 2013
- Yamane, Tsutomu; Murakami, Satoshi; Ikeguchi, Mitsunori
- Biochemistry, Vol. 52, Issue 43
Novel Strategies for the Treatment of Pseudomonas aeruginosa Infections
journal, February 2016
- Wagner, Stefanie; Sommer, Roman; Hinsberger, Stefan
- Journal of Medicinal Chemistry, Vol. 59, Issue 13
Crystal Structure of the Multidrug Exporter MexB from Pseudomonas aeruginosa
journal, May 2009
- Sennhauser, Gaby; Bukowska, Magdalena A.; Briand, Christophe
- Journal of Molecular Biology, Vol. 389, Issue 1
Canonical sampling through velocity rescaling
journal, January 2007
- Bussi, Giovanni; Donadio, Davide; Parrinello, Michele
- The Journal of Chemical Physics, Vol. 126, Issue 1
Pseudoatomic Structure of the Tripartite Multidrug Efflux Pump AcrAB-TolC Reveals the Intermeshing Cogwheel-like Interaction between AcrA and TolC
journal, February 2016
- Jeong, Hyeongseop; Kim, Jin-Sik; Song, Saemee
- Structure, Vol. 24, Issue 2
Within-host evolution of bacterial pathogens
journal, January 2016
- Didelot, Xavier; Walker, A. Sarah; Peto, Tim E.
- Nature Reviews Microbiology, Vol. 14, Issue 3
Computational Study of Correlated Domain Motions in the AcrB Efflux Transporter
journal, January 2015
- Schulz, Robert; Vargiu, Attilio V.; Ruggerone, Paolo
- BioMed Research International, Vol. 2015
Particle mesh Ewald: An N ⋅log( N ) method for Ewald sums in large systems
journal, June 1993
- Darden, Tom; York, Darrin; Pedersen, Lee
- The Journal of Chemical Physics, Vol. 98, Issue 12
Unilateral Access Regulation: Ground State Dynamics of the Pseudomonas aeruginosa Outer Membrane Efflux Duct OprM
journal, December 2012
- Koch, Dennis C.; Raunest, Martin; Harder, Tim
- Biochemistry, Vol. 52, Issue 1
Contribution of Outer Membrane Efflux Protein OprM to Antibiotic Resistance in Pseudomonas aeruginosa Independent of MexAB
journal, July 1998
- Zhao, Qixun; Li, Xian-Zhi; Srikumar, Ramakrishnan
- Antimicrobial Agents and Chemotherapy, Vol. 42, Issue 7
Drug export and allosteric coupling in a multidrug transporter revealed by molecular simulations
journal, November 2010
- Yao, Xin-Qiu; Kenzaki, Hiroo; Murakami, Satoshi
- Nature Communications, Vol. 1, Issue 1
Drug export and allosteric coupling in a multidrug transporter revealed by molecular simulations
journal, November 2010
- Yao, Xin-Qiu; Kenzaki, Hiroo; Murakami, Satoshi
- Nature Communications, Vol. 1, Issue 1
Molecular dynamics with coupling to an external bath
journal, October 1984
- Berendsen, H. J. C.; Postma, J. P. M.; van Gunsteren, W. F.
- The Journal of Chemical Physics, Vol. 81, Issue 8
Mechanism of coupling drug transport reactions located in two different membranes
journal, February 2015
- Zgurskaya, Helen I.; Weeks, Jon W.; Ntreh, Abigail T.
- Frontiers in Microbiology, Vol. 6
Understanding the mechanisms and drivers of antimicrobial resistance
journal, January 2016
- Holmes, Alison H.; Moore, Luke S. P.; Sundsfjord, Arnfinn
- The Lancet, Vol. 387, Issue 10014
Statistical Thermodynamics for Functionally Rotating Mechanism of the Multidrug Efflux Transporter AcrB
journal, February 2015
- Mishima, Hirokazu; Oshima, Hiraku; Yasuda, Satoshi
- The Journal of Physical Chemistry B, Vol. 119, Issue 8
Macroscopic conductivity of aqueous electrolyte solutions scales with ultrafast microscopic ion motions
text, January 2020
- Balos, Vasileios; Imoto, Sho; Netz, Roland R.
- Freie Universität Berlin
Polarizable Water Model for the Coarse-Grained MARTINI Force Field
journal, June 2010
- Yesylevskyy, Semen O.; Schäfer, Lars V.; Sengupta, Durba
- PLoS Computational Biology, Vol. 6, Issue 6
Opening the Channel: the Two Functional Interfaces of Pseudomonas aeruginosa OpmH with the Triclosan Efflux Pump TriABC
journal, September 2016
- Ntreh, Abigail T.; Weeks, Jon W.; Nickels, Logan M.
- Journal of Bacteriology, Vol. 198, Issue 23
Flexibility in a Drug Transport Accessory Protein: Molecular Dynamics Simulations of MexA
journal, July 2006
- Vaccaro, Loredana; Koronakis, Vassilis; Sansom, Mark S. P.
- Biophysical Journal, Vol. 91, Issue 2
Multidrug efflux transporter, AcrB—the pumping mechanism
journal, August 2008
- Murakami, S.
- Current Opinion in Structural Biology, Vol. 18, Issue 4
Fitting Periplasmic Membrane Fusion Proteins to Inner Membrane Transporters: Mutations That Enable Escherichia coli AcrA To Function with Pseudomonas aeruginosa MexB
journal, November 2007
- Krishnamoorthy, G.; Tikhonova, E. B.; Zgurskaya, H. I.
- Journal of Bacteriology, Vol. 190, Issue 2
Escherichia coli Peptidoglycan Structure and Mechanics as Predicted by Atomic-Scale Simulations
journal, February 2014
- Gumbart, James C.; Beeby, Morgan; Jensen, Grant J.
- PLoS Computational Biology, Vol. 10, Issue 2
Structure and Function of TolC: The Bacterial Exit Duct for Proteins and Drugs
journal, June 2004
- Koronakis, Vassilis; Eswaran, Jeyanthy; Hughes, Colin
- Annual Review of Biochemistry, Vol. 73, Issue 1
Molecular Dynamics Computer Simulations of Multidrug rnd Efflux Pumps
journal, February 2013
- Ruggerone, Paolo; Vargiu, Attilio V.; Collu, Francesca
- Computational and Structural Biotechnology Journal, Vol. 5, Issue 6
g_wham—A Free Weighted Histogram Analysis Implementation Including Robust Error and Autocorrelation Estimates
journal, November 2010
- Hub, Jochen S.; de Groot, Bert L.; van der Spoel, David
- Journal of Chemical Theory and Computation, Vol. 6, Issue 12
Bacterial Multidrug Efflux Transporters
journal, May 2014
- Delmar, Jared A.; Su, Chih-Chia; Yu, Edward W.
- Annual Review of Biophysics, Vol. 43, Issue 1
Advances in the molecular dynamics flexible fitting method for cryo-EM modeling
journal, May 2016
- McGreevy, Ryan; Teo, Ivan; Singharoy, Abhishek
- Methods, Vol. 100
Lipid14: The Amber Lipid Force Field
journal, January 2014
- Dickson, Callum J.; Madej, Benjamin D.; Skjevik, Åge A.
- Journal of Chemical Theory and Computation, Vol. 10, Issue 2
Drug Uptake Pathways of Multidrug Transporter AcrB Studied by Molecular Simulations and Site-Directed Mutagenesis Experiments
journal, May 2013
- Yao, Xin-Qiu; Kimura, Nobuhiro; Murakami, Satoshi
- Journal of the American Chemical Society, Vol. 135, Issue 20
Crystal Structure and Pair Potentials: A Molecular-Dynamics Study
journal, October 1980
- Parrinello, M.; Rahman, A.
- Physical Review Letters, Vol. 45, Issue 14
Generating stereochemically acceptable protein pathways
journal, September 2010
- Farrell, Daniel W.; Speranskiy, Kirill; Thorpe, M. F.
- Proteins: Structure, Function, and Bioinformatics, Vol. 78, Issue 14
Conformational Flexibility in the Multidrug Efflux System Protein AcrA
journal, March 2006
- Mikolosko, Jonathan; Bobyk, Kostyantyn; Zgurskaya, Helen I.
- Structure, Vol. 14, Issue 3
Crystal structure of the CusBA heavy-metal efflux complex of Escherichia coli
journal, February 2011
- Su, Chih-Chia; Long, Feng; Zimmermann, Michael T.
- Nature, Vol. 470, Issue 7335
Molecular dynamics-based refinement and validation for sub-5 Å cryo-electron microscopy maps
journal, July 2016
- Singharoy, Abhishek; Teo, Ivan; McGreevy, Ryan
- eLife, Vol. 5
Crystal structure of the CusBA heavy-metal efflux complex of Escherichia coli
journal, February 2011
- Su, Chih-Chia; Long, Feng; Zimmermann, Michael T.
- Nature, Vol. 470, Issue 7335
Assembly and Channel Opening of Outer Membrane Protein in Tripartite Drug Efflux Pumps of Gram-negative Bacteria
journal, February 2012
- Xu, Yongbin; Moeller, Arne; Jun, So-Young
- Journal of Biological Chemistry, Vol. 287, Issue 15
UniProt: the universal protein knowledgebase
journal, November 2016
- :(unav),
- Nucleic Acids Research, Vol. 45, Issue D1, p. D158-D169
Pseudomonas aeruginosa – a phenomenon of bacterial resistance
journal, September 2009
- Yordanov, Daniel; Strateva, Tanya
- Journal of Medical Microbiology, Vol. 58, Issue 9
Mechanistic Parallels in Bacterial and Human Multidrug Efflux Transporters
journal, October 2002
- Zgurskaya, H. I.; Nikaido, H.
- Current Protein & Peptide Science, Vol. 3, Issue 5
Assembly and Channel Opening in a Bacterial Drug Efflux Machine
journal, April 2008
- Bavro, Vassiliy N.; Pietras, Zbigniew; Furnham, Nicholas
- Molecular Cell, Vol. 30, Issue 1, p. 114-121
An overview of bacterial efflux pumps and computational approaches to study efflux pump inhibitors
journal, February 2016
- Jamshidi, Shirin; Sutton, J. Mark; Rahman, Khondaker M.
- Future Medicinal Chemistry, Vol. 8, Issue 2
Multidrug efflux pumps in Gram-negative bacteria and their role in antibiotic resistance
journal, October 2014
- Blair, Jessica MA; Richmond, Grace E.; Piddock, Laura JV
- Future Microbiology, Vol. 9, Issue 10
Advances in the molecular dynamics flexible fitting method for cryo-EM modeling
journal, May 2016
- McGreevy, Ryan; Teo, Ivan; Singharoy, Abhishek
- Methods, Vol. 100
Sequence co-evolution gives 3D contacts and structures of protein complexes
journal, September 2014
- Hopf, Thomas A.; Schärfe, Charlotta P. I.; Rodrigues, João P. G. L. M.
- eLife, Vol. 3
Improved side-chain torsion potentials for the Amber ff99SB protein force field
journal, January 2010
- Lindorff-Larsen, Kresten; Piana, Stefano; Palmo, Kim
- Proteins: Structure, Function, and Bioinformatics
The assembly and disassembly of the AcrAB-TolC three-component multidrug efflux pump
journal, September 2015
- Müller, Reinke Tobias; Pos, Klaas Martinus
- Biological Chemistry, Vol. 396, Issue 9-10
Crystal Structure of the Membrane Fusion Protein, MexA, of the Multidrug Transporter in Pseudomonas aeruginosa
journal, April 2004
- Akama, Hiroyuki; Matsuura, Takanori; Kashiwagi, Sachiko
- Journal of Biological Chemistry, Vol. 279, Issue 25
Assembly of the MexAB-OprM Multidrug Pump of Pseudomonas aeruginosa: Component Interactions Defined by the Study of Pump Mutant Suppressors
journal, June 2007
- Nehme, D.; Poole, K.
- Journal of Bacteriology, Vol. 189, Issue 17
Structural basis of RND-type multidrug exporters
journal, April 2015
- Yamaguchi, Akihito; Nakashima, Ryosuke; Sakurai, Keisuke
- Frontiers in Microbiology, Vol. 6
P-LINCS: A Parallel Linear Constraint Solver for Molecular Simulation
journal, December 2007
- Hess, Berk
- Journal of Chemical Theory and Computation, Vol. 4, Issue 1
The MARTINI Force Field: Coarse Grained Model for Biomolecular Simulations
journal, July 2007
- Marrink, Siewert J.; Risselada, H. Jelger; Yefimov, Serge
- The Journal of Physical Chemistry B, Vol. 111, Issue 27
Crystal Structure of the Drug Discharge Outer Membrane Protein, OprM, of Pseudomonas aeruginosa : DUAL MODES OF MEMBRANE ANCHORING AND OCCLUDED CAVITY END
journal, October 2004
- Akama, Hiroyuki; Kanemaki, Misa; Yoshimura, Masato
- Journal of Biological Chemistry, Vol. 279, Issue 51
Computational Methodologies for Real-Space Structural Refinement of Large Macromolecular Complexes
journal, July 2016
- Goh, Boon Chong; Hadden, Jodi A.; Bernardi, Rafael C.
- Annual Review of Biophysics, Vol. 45, Issue 1
Cryo-Transmission Electron Microscopy of Frozen-Hydrated Sections of Escherichia coli and Pseudomonas aeruginosa
journal, October 2003
- Matias, V. R. F.; Al-Amoudi, A.; Dubochet, J.
- Journal of Bacteriology, Vol. 185, Issue 20
GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit
journal, February 2013
- Pronk, Sander; Páll, Szilárd; Schulz, Roland
- Bioinformatics, Vol. 29, Issue 7
Multidrug-Resistant Gram-Negative Bacterial Infections in the Hospital Setting: Overview, Implications for Clinical Practice, and Emerging Treatment Options
journal, July 2016
- Cerceo, Elizabeth; Deitelzweig, Steven B.; Sherman, Bradley M.
- Microbial Drug Resistance, Vol. 22, Issue 5
Isolation and characterization of antibiotic-resistant bacteria from pharmaceutical industrial wastewaters
journal, December 2015
- Tahrani, Leyla; Soufi, Leila; Mehri, Ines
- Microbial Pathogenesis, Vol. 89
A data-driven approach to modeling the tripartite structure of multidrug resistance efflux pumps: Modeling of Multidrug Resistance Efflux Pumps
journal, November 2014
- Phillips, Joshua L.; Gnanakaran, S.
- Proteins: Structure, Function, and Bioinformatics, Vol. 83, Issue 1
Structures of sequential open states in a symmetrical opening transition of the TolC exit duct
journal, January 2011
- Pei, Xue-Yuan; Hinchliffe, Philip; Symmons, Martyn F.
- Proceedings of the National Academy of Sciences, Vol. 108, Issue 5
Robust and accurate prediction of residue–residue interactions across protein interfaces using evolutionary information
journal, May 2014
- Ovchinnikov, Sergey; Kamisetty, Hetunandan; Baker, David
- eLife, Vol. 3
Pseudomonas aeruginosa: all roads lead to resistance
journal, August 2011
- Breidenstein, Elena B. M.; de la Fuente-Núñez, César; Hancock, Robert E. W.
- Trends in Microbiology, Vol. 19, Issue 8
The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria
journal, March 2015
- Li, Xian-Zhi; Plésiat, Patrick; Nikaido, Hiroshi
- Clinical Microbiology Reviews, Vol. 28, Issue 2
Resistance Mechanisms in Pseudomonas aeruginosa and Other Nonfermentative Gram‐Negative Bacteria
journal, August 1998
- Hancock, Robert E. W.
- Clinical Infectious Diseases, Vol. 27, Issue s1
AcrA is a highly asymmetric protein capable of spanning the periplasm 1 1Edited by I. B. Holland
journal, January 1999
- Zgurskaya, Helen I.; Nikaido, Hiroshi
- Journal of Molecular Biology, Vol. 285, Issue 1
RETRACTED ARTICLE: Profile of Virulence Factors in the Multi-Drug Resistant Pseudomonas aeruginosa Strains of Human Urinary Tract Infections (UTI)
journal, December 2015
- Habibi, Asghar; Honarmand, Ramin
- Iranian Red Crescent Medical Journal, Vol. 17, Issue 12
Antibiotic efflux mechanisms
journal, January 1999
- Nikaido, Hiroshi; Zgurskaya, Helen I.
- Current Opinion in Infectious Diseases, Vol. 12, Issue 6
Coupling of remote alternating-access transport mechanisms for protons and substrates in the multidrug efflux pump AcrB
journal, September 2014
- Eicher, Thomas; Seeger, Markus A.; Anselmi, Claudio
- eLife, Vol. 3
Pseudoatomic Structure of the Tripartite Multidrug Efflux Pump AcrAB-TolC Reveals the Intermeshing Cogwheel-like Interaction between AcrA and TolC
journal, February 2016
- Jeong, Hyeongseop; Kim, Jin-Sik; Song, Saemee
- Structure, Vol. 24, Issue 2
Outer membrane permeability and antibiotic resistance
journal, May 2009
- Delcour, Anne H.
- Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1794, Issue 5
Molecular Dynamics and NMR Spectroscopy Studies of E. coli Lipopolysaccharide Structure and Dynamics
journal, September 2013
- Wu, Emilia L.; Engström, Olof; Jo, Sunhwan
- Biophysical Journal, Vol. 105, Issue 6
Structure of the AcrAB–TolC multidrug efflux pump
journal, April 2014
- Du, Dijun; Wang, Zhao; James, Nathan R.
- Nature, Vol. 509, Issue 7501
Structure, mechanism and cooperation of bacterial multidrug transporters
journal, August 2015
- Du, Dijun; van Veen, Hendrik W.; Murakami, Satoshi
- Current Opinion in Structural Biology, Vol. 33
Computational Study of Correlated Domain Motions in the AcrB Efflux Transporter
journal, January 2015
- Schulz, Robert; Vargiu, Attilio V.; Ruggerone, Paolo
- BioMed Research International, Vol. 2015
Polarizable Water Model for the Coarse-Grained MARTINI Force Field
journal, June 2010
- Yesylevskyy, Semen O.; Schäfer, Lars V.; Sengupta, Durba
- PLoS Computational Biology, Vol. 6, Issue 6
Molecular Dynamics Computer Simulations of Multidrug rnd Efflux Pumps
journal, February 2013
- Ruggerone, Paolo; Vargiu, Attilio V.; Collu, Francesca
- Computational and Structural Biotechnology Journal, Vol. 5, Issue 6
The effects of active efflux pumps on antibiotic resistance in Pseudomonas aeruginosa
journal, June 2014
- Terzi, Huseyin Agah; Kulah, Canan; Ciftci, İhsan Hakkı
- World Journal of Microbiology and Biotechnology, Vol. 30, Issue 10
Nonphysical sampling distributions in Monte Carlo free-energy estimation: Umbrella sampling
journal, February 1977
- Torrie, G. M.; Valleau, J. P.
- Journal of Computational Physics, Vol. 23, Issue 2
Antibiotic resistance in Pseudomonas aeruginosa and alternative therapeutic options
journal, January 2016
- Chatterjee, Maitrayee; Anju, C. P.; Biswas, Lalitha
- International Journal of Medical Microbiology, Vol. 306, Issue 1
Unilateral Access Regulation: Ground State Dynamics of the Pseudomonas aeruginosa Outer Membrane Efflux Duct OprM
journal, December 2012
- Koch, Dennis C.; Raunest, Martin; Harder, Tim
- Biochemistry, Vol. 52, Issue 1
Structure of reconstituted bacterial membrane efflux pump by cryo-electron tomography
journal, October 2010
- Trépout, Sylvain; Taveau, Jean-Christophe; Benabdelhak, Houssain
- Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1798, Issue 10
Structure of reconstituted bacterial membrane efflux pump by cryo-electron tomography
journal, October 2010
- Trépout, Sylvain; Taveau, Jean-Christophe; Benabdelhak, Houssain
- Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1798, Issue 10
Residue – Residue Potentials with a Favorable Contact Pair Term and an Unfavorable High Packing Density Term, for Simulation and Threading
journal, March 1996
- Miyazawa, Sanzo; Jernigan, Robert L.
- Journal of Molecular Biology, Vol. 256, Issue 3
Interactions underlying assembly of the Escherichia coli AcrAB-TolC multidrug efflux system: Multidrug efflux system assembly
journal, June 2004
- Touzé, Thierry; Eswaran, Jeyanthy; Bokma, Evert
- Molecular Microbiology, Vol. 53, Issue 2
Functional Rotation Induced by Alternating Protonation States in the Multidrug Transporter AcrB: All-Atom Molecular Dynamics Simulations
journal, October 2013
- Yamane, Tsutomu; Murakami, Satoshi; Ikeguchi, Mitsunori
- Biochemistry, Vol. 52, Issue 43
Sequential Mechanism of Assembly of Multidrug Efflux Pump AcrAB-TolC
journal, April 2011
- Tikhonova, Elena B.; Yamada, Yoichi; Zgurskaya, Helen I.
- Chemistry & Biology, Vol. 18, Issue 4
Crystal Structure of the Multidrug Exporter MexB from Pseudomonas aeruginosa
journal, May 2009
- Sennhauser, Gaby; Bukowska, Magdalena A.; Briand, Christophe
- Journal of Molecular Biology, Vol. 389, Issue 1
AcrA is a highly asymmetric protein capable of spanning the periplasm 1 1Edited by I. B. Holland
journal, January 1999
- Zgurskaya, Helen I.; Nikaido, Hiroshi
- Journal of Molecular Biology, Vol. 285, Issue 1
Catch me if you can: a biotinylated proteoliposome affinity assay for the investigation of assembly of the MexA-MexB-OprM efflux pump from Pseudomonas aeruginosa
journal, June 2015
- Ntsogo Enguéné, Véronique Yvette; Verchère, Alice; Phan, Gilles
- Frontiers in Microbiology, Vol. 6
Interaction of antibacterial compounds with RND efflux pumps in Pseudomonas aeruginosa
journal, July 2015
- Dreier, Jürg; Ruggerone, Paolo
- Frontiers in Microbiology, Vol. 6
Functional replacement of OprJ by OprM in the MexCD-OprJ multidrug efflux system of Pseudomonas aeruginosa
journal, August 1998
- Gotoh, Naomasa; Tsujimoto, Hideto; Nomura, Atsuko
- FEMS Microbiology Letters, Vol. 165, Issue 1
Generating stereochemically acceptable protein pathways
journal, September 2010
- Farrell, Daniel W.; Speranskiy, Kirill; Thorpe, M. F.
- Proteins: Structure, Function, and Bioinformatics, Vol. 78, Issue 14
Conformational Flexibility in the Multidrug Efflux System Protein AcrA
journal, March 2006
- Mikolosko, Jonathan; Bobyk, Kostyantyn; Zgurskaya, Helen I.
- Structure, Vol. 14, Issue 3
Multidrug Resistant and Extensively Drug Resistant Bacteria: A Study
journal, January 2016
- Basak, Silpi; Singh, Priyanka; Rajurkar, Monali
- Journal of Pathogens, Vol. 2016
Drug Uptake Pathways of Multidrug Transporter AcrB Studied by Molecular Simulations and Site-Directed Mutagenesis Experiments
journal, May 2013
- Yao, Xin-Qiu; Kimura, Nobuhiro; Murakami, Satoshi
- Journal of the American Chemical Society, Vol. 135, Issue 20
Molecular Dynamics and NMR Spectroscopy Studies of E. coli Lipopolysaccharide Structure and Dynamics
journal, September 2013
- Wu, Emilia L.; Engström, Olof; Jo, Sunhwan
- Biophysical Journal, Vol. 105, Issue 6
Antibiotic resistance in Pseudomonas aeruginosa and alternative therapeutic options
journal, January 2016
- Chatterjee, Maitrayee; Anju, C. P.; Biswas, Lalitha
- International Journal of Medical Microbiology, Vol. 306, Issue 1
New OprM structure highlighting the nature of the N-terminal anchor
journal, July 2015
- Monlezun, Laura; Phan, Gilles; Benabdelhak, Houssain
- Frontiers in Microbiology, Vol. 6
LAMBADA and InflateGRO2: Efficient Membrane Alignment and Insertion of Membrane Proteins for Molecular Dynamics Simulations
journal, September 2012
- Schmidt, Thomas H.; Kandt, Christian
- Journal of Chemical Information and Modeling, Vol. 52, Issue 10
Molecular dynamics flexible fitting: A practical guide to combine cryo-electron microscopy and X-ray crystallography
journal, October 2009
- Trabuco, Leonardo G.; Villa, Elizabeth; Schreiner, Eduard
- Methods, Vol. 49, Issue 2
Escherichia coli Peptidoglycan Structure and Mechanics as Predicted by Atomic-Scale Simulations
journal, February 2014
- Gumbart, James C.; Beeby, Morgan; Jensen, Grant J.
- PLoS Computational Biology, Vol. 10, Issue 2
Electrophysiological Behavior of the TolC Channel-Tunnel in Planar Lipid Bilayers
journal, January 2002
- Andersen, C.; Hughes, C.; Koronakis, V.
- Journal of Membrane Biology, Vol. 185, Issue 1
The MARTINI Force Field: Coarse Grained Model for Biomolecular Simulations
journal, July 2007
- Marrink, Siewert J.; Risselada, H. Jelger; Yefimov, Serge
- The Journal of Physical Chemistry B, Vol. 111, Issue 27
Breaking the Spell: Combating Multidrug Resistant ‘Superbugs’
journal, February 2016
- Khan, Shahper N.; Khan, Asad U.
- Frontiers in Microbiology, Vol. 7
Structures of sequential open states in a symmetrical opening transition of the TolC exit duct
journal, January 2011
- Pei, Xue-Yuan; Hinchliffe, Philip; Symmons, Martyn F.
- Proceedings of the National Academy of Sciences, Vol. 108, Issue 5
Structure and Function of TolC: The Bacterial Exit Duct for Proteins and Drugs
journal, June 2004
- Koronakis, Vassilis; Eswaran, Jeyanthy; Hughes, Colin
- Annual Review of Biochemistry, Vol. 73, Issue 1
Multiple conformational states and gate opening of outer membrane protein TolC revealed by molecular dynamics simulations: MD Simulation of TolC
journal, June 2014
- Wang, Beibei; Weng, Jingwei; Wang, Wenning
- Proteins: Structure, Function, and Bioinformatics, Vol. 82, Issue 9
Structural and Dynamical Insights into the Opening Mechanism of P. aeruginosa OprM Channel
journal, March 2010
- Phan, Gilles; Benabdelhak, Houssain; Lascombe, Marie-Bernard
- Structure, Vol. 18, Issue 4
GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit
journal, February 2013
- Pronk, Sander; Páll, Szilárd; Schulz, Roland
- Bioinformatics, Vol. 29, Issue 7
Permeability Barrier of Gram-Negative Cell Envelopes and Approaches To Bypass It
journal, August 2015
- Zgurskaya, Helen I.; López, Cesar A.; Gnanakaran, S.
- ACS Infectious Diseases, Vol. 1, Issue 11
Molecular dynamics with coupling to an external bath
journal, October 1984
- Berendsen, H. J. C.; Postma, J. P. M.; van Gunsteren, W. F.
- The Journal of Chemical Physics, Vol. 81, Issue 8
Statistical Thermodynamics for Functionally Rotating Mechanism of the Multidrug Efflux Transporter AcrB
journal, February 2015
- Mishima, Hirokazu; Oshima, Hiraku; Yasuda, Satoshi
- The Journal of Physical Chemistry B, Vol. 119, Issue 8
Mechanism of coupling drug transport reactions located in two different membranes
journal, February 2015
- Zgurskaya, Helen I.; Weeks, Jon W.; Ntreh, Abigail T.
- Frontiers in Microbiology, Vol. 6
Pseudomonas aeruginosa: all roads lead to resistance
journal, August 2011
- Breidenstein, Elena B. M.; de la Fuente-Núñez, César; Hancock, Robert E. W.
- Trends in Microbiology, Vol. 19, Issue 8
Ultra-fast FFT protein docking on graphics processors
journal, August 2010
- Ritchie, David W.; Venkatraman, Vishwesh
- Bioinformatics, Vol. 26, Issue 19
P-LINCS: A Parallel Linear Constraint Solver for Molecular Simulation
journal, December 2007
- Hess, Berk
- Journal of Chemical Theory and Computation, Vol. 4, Issue 1
Structure of the MacAB–TolC ABC-type tripartite multidrug efflux pump
journal, May 2017
- Fitzpatrick, Anthony W. P.; Llabrés, Salomé; Neuberger, Arthur
- Nature Microbiology, Vol. 2, Issue 7
The Importance of Efflux Systems in Antibiotic Resistance and Efflux Pump Inhibitors in the Management of Resistance [Antibiyotik Direncinde Dışa Atım Sistemlerinin ve Dirençle Mücadelede Dışa Atım Pompa İnhibitörlerinin Önemi]
journal, April 2015
- AygÜL, Abdurrahman
- Mikrobiyoloji Bulteni, Vol. 49, Issue 2
Pseudomonas aeruginosa – a phenomenon of bacterial resistance
journal, September 2009
- Yordanov, Daniel; Strateva, Tanya
- Journal of Medical Microbiology, Vol. 58, Issue 9
Contribution of the MexX-MexY-OprM Efflux System to Intrinsic Resistance in Pseudomonas aeruginosa
journal, September 2000
- Masuda, N.; Sakagawa, E.; Ohya, S.
- Antimicrobial Agents and Chemotherapy, Vol. 44, Issue 9
Permeability of Pseudomonas aeruginosa outer membrane to hydrophilic solutes
journal, November 1982
- Yoshimura, F.; Nikaido, H.
- Journal of Bacteriology, Vol. 152, Issue 2
HHblits: lightning-fast iterative protein sequence searching by HMM-HMM alignment
journal, December 2011
- Remmert, Michael; Biegert, Andreas; Hauser, Andreas
- Nature Methods, Vol. 9, Issue 2
Works referencing / citing this record:
AcrB: a mean, keen, drug efflux machine
journal, September 2019
- Kobylka, Jessica; Kuth, Miriam S.; Müller, Reinke T.
- Annals of the New York Academy of Sciences, Vol. 1459, Issue 1