Cryo-EM structure of multidrug efflux pump MexAB-OprM (60 degree state)Cryo-EM structure of multidrug efflux pump MexAB-OprM (60 degree state)

Structural highlights

6iol is a 12 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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Function

[MEXA_PSEAE] The periplasmic linker component of the MexAB-OprM efflux system that confers multidrug resistance. Also functions as the major efflux pump for n-hexane and p-xylene efflux. Over-expression of the pump increases antibiotic and solvent efflux capacities. Required for assembly of the MexA/MexB/OprM complex. Implicated in the secretion of the siderophore pyoverdine.[1] [2] [3] The ability to export antibiotics and solvents is dramatically decreased in the presence of the proton conductor carbonyl cyanide m-chlorophenylhydrazone (CCCP), showing that an energized inner membrane is required for efflux. It is thought that the MexB subunit is a proton antiporter.[4] [5] [6] [MEXB_PSEAE] The inner membrane transporter component of the MexAB-OprM efflux system that confers multidrug resistance. Also functions as the major efflux pump for n-hexane and p-xylene efflux. Over-expression of the pump increases antibiotic and solvent efflux capacities. Implicated in the secretion of the siderophore pyoverdine.[7] [8] [9] The ability to export antibiotics and solvents is dramatically decreased in the presence of the proton conductor carbonyl cyanide m-chlorophenylhydrazone (CCCP), showing that an energized inner membrane is required for efflux. It is thought that the MexB subunit is a proton antiporter.[10] [11] [12] [OPRM_PSEAE] The outer membrane component of the MexAB-OprM efflux system that confers multidrug resistance. Also functions as the major efflux pump for n-hexane and p-xylene efflux. Over-expression of the pump increases antibiotic and solvent efflux capacities. Can replace the OprJ outer membrane component of the MexCD-OprJ pump; the antibiotics exported are those exported by the intact MexCD pump, showing that efflux substrate specificity is not conferred by this component. Serves as the outer membrane component for the MexXY efflux system. Implicated in the secretion of the siderophore pyoverdine. OprM is probably involved in the efflux of the siderophore across the outer membrane.[13] [14] [15] [16] [17] The ability to export antibiotics and solvents is dramatically decreased in the presence of the proton conductor carbonyl cyanide m-chlorophenylhydrazone (CCCP), showing that an energized inner membrane is required for efflux. It is thought that the MexB subunit is a proton antiporter.[18] [19] [20] [21] [22]

References

  1. Poole K, Krebes K, McNally C, Neshat S. Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon. J Bacteriol. 1993 Nov;175(22):7363-72. PMID:8226684
  2. Li XZ, Nikaido H, Poole K. Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1995 Sep;39(9):1948-53. PMID:8540696
  3. Li XZ, Zhang L, Poole K. Role of the multidrug efflux systems of Pseudomonas aeruginosa in organic solvent tolerance. J Bacteriol. 1998 Jun;180(11):2987-91. PMID:9603892
  4. Poole K, Krebes K, McNally C, Neshat S. Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon. J Bacteriol. 1993 Nov;175(22):7363-72. PMID:8226684
  5. Li XZ, Nikaido H, Poole K. Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1995 Sep;39(9):1948-53. PMID:8540696
  6. Li XZ, Zhang L, Poole K. Role of the multidrug efflux systems of Pseudomonas aeruginosa in organic solvent tolerance. J Bacteriol. 1998 Jun;180(11):2987-91. PMID:9603892
  7. Poole K, Krebes K, McNally C, Neshat S. Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon. J Bacteriol. 1993 Nov;175(22):7363-72. PMID:8226684
  8. Li XZ, Nikaido H, Poole K. Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1995 Sep;39(9):1948-53. PMID:8540696
  9. Li XZ, Zhang L, Poole K. Role of the multidrug efflux systems of Pseudomonas aeruginosa in organic solvent tolerance. J Bacteriol. 1998 Jun;180(11):2987-91. PMID:9603892
  10. Poole K, Krebes K, McNally C, Neshat S. Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon. J Bacteriol. 1993 Nov;175(22):7363-72. PMID:8226684
  11. Li XZ, Nikaido H, Poole K. Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1995 Sep;39(9):1948-53. PMID:8540696
  12. Li XZ, Zhang L, Poole K. Role of the multidrug efflux systems of Pseudomonas aeruginosa in organic solvent tolerance. J Bacteriol. 1998 Jun;180(11):2987-91. PMID:9603892
  13. Poole K, Krebes K, McNally C, Neshat S. Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon. J Bacteriol. 1993 Nov;175(22):7363-72. PMID:8226684
  14. Li XZ, Nikaido H, Poole K. Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1995 Sep;39(9):1948-53. PMID:8540696
  15. Srikumar R, Li XZ, Poole K. Inner membrane efflux components are responsible for beta-lactam specificity of multidrug efflux pumps in Pseudomonas aeruginosa. J Bacteriol. 1997 Dec;179(24):7875-81. PMID:9401051
  16. Li XZ, Zhang L, Poole K. Role of the multidrug efflux systems of Pseudomonas aeruginosa in organic solvent tolerance. J Bacteriol. 1998 Jun;180(11):2987-91. PMID:9603892
  17. Masuda N, Sakagawa E, Ohya S, Gotoh N, Tsujimoto H, Nishino T. Contribution of the MexX-MexY-oprM efflux system to intrinsic resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2000 Sep;44(9):2242-6. PMID:10952562
  18. Poole K, Krebes K, McNally C, Neshat S. Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon. J Bacteriol. 1993 Nov;175(22):7363-72. PMID:8226684
  19. Li XZ, Nikaido H, Poole K. Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1995 Sep;39(9):1948-53. PMID:8540696
  20. Srikumar R, Li XZ, Poole K. Inner membrane efflux components are responsible for beta-lactam specificity of multidrug efflux pumps in Pseudomonas aeruginosa. J Bacteriol. 1997 Dec;179(24):7875-81. PMID:9401051
  21. Li XZ, Zhang L, Poole K. Role of the multidrug efflux systems of Pseudomonas aeruginosa in organic solvent tolerance. J Bacteriol. 1998 Jun;180(11):2987-91. PMID:9603892
  22. Masuda N, Sakagawa E, Ohya S, Gotoh N, Tsujimoto H, Nishino T. Contribution of the MexX-MexY-oprM efflux system to intrinsic resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2000 Sep;44(9):2242-6. PMID:10952562

6iol, resolution 3.76Å

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