Configuration Flipping in Distal Pocket of Multidrug Transporter MexB Impacts the Efflux Inhibitory Mechanism
نویسندگان
چکیده
منابع مشابه
Identification of essential charged residues in transmembrane segments of the multidrug transporter MexB of Pseudomonas aeruginosa.
The MexABM efflux pump exports structurally diverse xenobiotics, utilizing the proton electrochemical gradient to confer drug resistance on Pseudomonas aeruginosa. The MexB subunit traverses the inner membrane 12 times and has two, two, and one charged residues in putative transmembrane segments 2 (TMS-2), TMS-4, and TMS-10, respectively. All five residues were mutated, and MexB function was ev...
متن کاملsiRNA-mediated gene silencing of MexB from the MexA-MexB-OprM efflux pump in Pseudomonas aeruginosa
To gain insights into the effect of MexB gene under the short interfering RNA (siRNA), we synthesized 21 bp siRNA duplexes against the MexB gene. RT-PCR was performed to determine whether the siRNA inhibited the expression of MexB mRNA. Changes in antibiotic susceptibility in response to siRNA were measured by the E-test method. The efficacy of siRNAs was determined in a murine model of chronic...
متن کاملExpression, detergent solubilization, and purification of a membrane transporter, the MexB multidrug resistance protein.
Multidrug resistance (MDR), the ability of a cancer cell or pathogen to be resistant to a wide range of structurally and functionally unrelated anti-cancer drugs or antibiotics, is a current serious problem in public health. This multidrug resistance is largely due to energy-dependent drug efflux pumps. The pumps expel anti-cancer drugs or antibiotics into the external medium, lowering their in...
متن کاملPromiscuous partnering and independent activity of MexB, the multidrug transporter protein from Pseudomonas aeruginosa.
The MexAB-OprM drug efflux pump is central to multidrug resistance of Pseudomonas aeruginosa. The ability of the tripartite protein to confer drug resistance on the pathogen is crucially dependent on the presence of all three proteins of the complex. However, the role of each protein in the formation of the intact functional complex is not well understood. One of the key questions relates to th...
متن کاملInteraction of the MexA and MexB components of the MexAB-OprM multidrug efflux system of Pseudomonas aeruginosa: identification of MexA extragenic suppressors of a T578I mutation in MexB.
A T578I mutation in MexB compromised the protein's contribution to antimicrobial resistance and negatively impacted its interaction with MexA. Mutations causing single amino acid changes in the C-terminal domain of MexA (R221H, L245F, E254K, and V259I) suppressed the antimicrobial susceptibility of a MexB(T578I)-expressing Pseudomonas aeruginosa strain and restored a MexA interaction with MexB(...
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ژورنال
عنوان ژورنال: ChemPhysChem
سال: 2020
ISSN: 1439-4235,1439-7641
DOI: 10.1002/cphc.202000947