Journal article
Manipulating the drug/proton antiport stoichiometry of the secondary multidrug transporter MdfA
Proceedings of the National Academy of Sciences - PNAS, Vol.109(31), pp.12473-12478
07/31/2012
DOI: 10.1073/pnas.1203632109
PMCID: PMC3411955
PMID: 22802625
Abstract
Multidrug transporters are integral membrane proteins that use cellular energy to actively extrude antibiotics and other toxic compounds from cells. The multidrug/proton antiporter MdfA from Escherichia coli exchanges monovalent cationic substrates for protons with a stoichiometry of 1, meaning that it translocates only one proton per antiport cycle. This may explain why transport of divalent cationic drugs by MdfA is energetically unfavorable. Remarkably, however, we show that MdfA can be easily converted into a divalent cationic drug/>= 2 proton-antiporter, either by random mutagenesis or by rational design. The results suggest that exchange of divalent cationic drugs with two (or more) protons requires an additional acidic residue in the multidrug recognition pocket of MdfA. This outcome further illustrates the exceptional promiscuous capabilities of multidrug transporters.
Details
- Title: Subtitle
- Manipulating the drug/proton antiport stoichiometry of the secondary multidrug transporter MdfA
- Creators
- Osnat Tirosh - Weizmann Institute of ScienceNadejda Sigal - Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, IsraelAmir Gelman - Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, IsraelNadav Sahar - Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, IsraelNir Fluman - Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, IsraelShira Siemion - Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, IsraelEitan Bibi - Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.109(31), pp.12473-12478
- DOI
- 10.1073/pnas.1203632109
- PMID
- 22802625
- PMCID
- PMC3411955
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- Natl Acad Sciences
- Number of pages
- 6
- Grant note
- 1128/06 / Israel Science Foundation
- Language
- English
- Date published
- 07/31/2012
- Academic Unit
- Gastroenterology and Hepatology; Internal Medicine
- Record Identifier
- 9984359917102771
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