6Z12

Salmonella AcrB solubilised in the SMA copolymer

Summary for 6Z12

• Entry DOI: 10.2210/pdb6z12/pdb
• EMDB information: 4460
• Descriptor: Efflux pump membrane transporter (1 entity in total)
• Functional Keywords: acrb, membrane protein
• Biological source: Salmonella enterica I
• Total number of polymer chains: 3
• Total formula weight: 341277.68

Authors

Muench, s.p.,Johnson, R.M. (deposition date: 2020-05-11, release date: 2020-07-22, Last modification date: 2024-05-15)

Primary citation

Johnson, R.M.,Fais, C.,Parmar, M.,Cheruvara, H.,Marshall, R.L.,Hesketh, S.J.,Feasey, M.C.,Ruggerone, P.,Vargiu, A.V.,Postis, V.L.G.,Muench, S.P.,Bavro, V.N.
Cryo-EM Structure and Molecular Dynamics Analysis of the Fluoroquinolone Resistant Mutant of the AcrB Transporter fromSalmonella.
Microorganisms, 8:-, 2020

PubMed Abstract: is an important genus of Gram-negative pathogens, treatment of which has become problematic due to increases in antimicrobial resistance. This is partly attributable to the overexpression of tripartite efflux pumps, particularly the constitutively expressed AcrAB-TolC. Despite its clinical importance, the structure of the AcrB transporter remained unknown to-date, with much of our structural understanding coming from the orthologue. Here, by taking advantage of the styrene maleic acid (SMA) technology to isolate membrane proteins with closely associated lipids, we report the very first experimental structure of AcrB transporter. Furthermore, this novel structure provides additional insight into mechanisms of drug efflux as it bears the mutation (G288D), originating from a clinical isolate of Typhimurium presenting an increased resistance to fluoroquinolones. Experimental data are complemented by state-of-the-art molecular dynamics (MD) simulations on both the wild type and G288D variant of AcrB. Together, these reveal several important differences with respect to the protein, providing insights into the role of the G288D mutation in increasing drug efflux and extending our understanding of the mechanisms underlying antibiotic resistance.

PubMed: 32585951
DOI: 10.3390/microorganisms8060943

Experimental method

ELECTRON MICROSCOPY (4.6 Å)