4ziv

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Crystal structure of AcrB triple mutant in P21 space groupCrystal structure of AcrB triple mutant in P21 space group

Structural highlights

4ziv is a 6 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.16Å
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

Gram-negative bacteria such as E. coli use tripartite efflux pumps such as AcrAB-TolC to expel antibiotics and noxious compounds. A key feature of the inner membrane transporter component, AcrB, is a short stretch of residues known as the gate/switch loop that divides the proximal and distal substrate binding pockets. Amino acid substitutions of the gate loop are known to decrease antibiotic resistance conferred by AcrB. Here we present two new AcrB gate loop variants, the first stripped of its bulky side chains, and a second in which the gate loop is removed entirely. By determining the crystal structures of the variant AcrB proteins in the presence and absence of erythromycin and assessing their ability to confer erythromycin tolerance, we demonstrate that the gate loop is important for AcrB export activity but is not required for erythromycin binding.

Structures of Gate Loop Variants of the AcrB Drug Efflux Pump Bound by Erythromycin Substrate.,Ababou A, Koronakis V PLoS One. 2016 Jul 12;11(7):e0159154. doi: 10.1371/journal.pone.0159154., eCollection 2016. PMID:27403665[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. 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
  2. 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
  3. 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
  4. Ababou A, Koronakis V. Structures of Gate Loop Variants of the AcrB Drug Efflux Pump Bound by Erythromycin Substrate. PLoS One. 2016 Jul 12;11(7):e0159154. doi: 10.1371/journal.pone.0159154., eCollection 2016. PMID:27403665 doi:http://dx.doi.org/10.1371/journal.pone.0159154

4ziv, resolution 3.16Å

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