| Structural highlights
5jmn is a 5 chain structure with sequence from Escherichia coli K-12 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.5Å |
| Ligands: | , , , , , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
ACRB_ECOLI AcrAB is a drug efflux protein with a broad substrate specificity.[1] [2] [3]
Publication Abstract from PubMed
The deployment of multidrug efflux pumps is a powerful defence mechanism for Gram-negative bacterial cells when exposed to antimicrobial agents. The major multidrug efflux transport system in Escherichia coli, AcrAB-TolC, is a tripartite system using the proton-motive force as an energy source. The polyspecific substrate-binding module AcrB uses various pathways to sequester drugs from the periplasm and outer leaflet of the inner membrane. Here we report the asymmetric AcrB structure in complex with fusidic acid at a resolution of 2.5 A and mutational analysis of the putative fusidic acid binding site at the transmembrane domain. A groove shaped by the interface between transmembrane helix 1 (TM1) and TM2 specifically binds fusidic acid and other lipophilic carboxylated drugs. We propose that these bound drugs are actively displaced by an upward movement of TM2 towards the AcrB periplasmic porter domain in response to protonation events in the transmembrane domain.
Transport of lipophilic carboxylates is mediated by transmembrane helix 2 in multidrug transporter AcrB.,Oswald C, Tam HK, Pos KM Nat Commun. 2016 Dec 16;7:13819. doi: 10.1038/ncomms13819. PMID:27982032[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Murakami S, Nakashima R, Yamashita E, Matsumoto T, Yamaguchi A. Crystal structures of a multidrug transporter reveal a functionally rotating mechanism. Nature. 2006 Sep 14;443(7108):173-9. Epub 2006 Aug 16. PMID:16915237 doi:10.1038/nature05076
- ↑ Seeger MA, Schiefner A, Eicher T, Verrey F, Diederichs K, Pos KM. Structural asymmetry of AcrB trimer suggests a peristaltic pump mechanism. Science. 2006 Sep 1;313(5791):1295-8. PMID:16946072 doi:313/5791/1295
- ↑ Sennhauser G, Amstutz P, Briand C, Storchenegger O, Grutter MG. Drug export pathway of multidrug exporter AcrB revealed by DARPin inhibitors. PLoS Biol. 2007 Jan;5(1):e7. PMID:17194213 doi:10.1371/journal.pbio.0050007
- ↑ Oswald C, Tam HK, Pos KM. Transport of lipophilic carboxylates is mediated by transmembrane helix 2 in multidrug transporter AcrB. Nat Commun. 2016 Dec 16;7:13819. doi: 10.1038/ncomms13819. PMID:27982032 doi:http://dx.doi.org/10.1038/ncomms13819
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