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ATP-binding cassette transporters (ABC-transporter) superfamily

  • Multicomponent, Multidomain system consist of more than 1000 residues with 12 spanners (6+6).
  • Widely distributed in Bacteria, Archaea and Eukaryotes.
  • Most sequenced members >500.
  • Well characterized members: MalEFGH, CFTR, P glycoprotein.
  • Consist of >30 families responsible for efflux of drugs, antibiotics, vitamins, sugar, iron complexes etc.
  • Specific to hydrophobic molecules.
  • Widely distributed and mainly responsible for drug efflux in Eukaryotes.
Reference:Lubelski (2007) Distribution and Physiology of ABC-Type Transporters Contributing to Multidrug Resistance in Bacteria MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWs 71: 463–476






Major Facilitator Superfamily (MFS)

  • Utilize antiporter, symporter or uniporter mechanisms.
  • Ancient family like ABC, consist of efflux  of more than 17 families specific for efflux of drugs, antibiotics, sugars, anions etc.
  • Most functionally diverse, energized by electrochemical proton gradient found in Archaea, Bacteria and Eukaryotes.
  • Well characterized members: LacY, Glut1, EmrD, LmrP, Mdfa, TetB ect.
  • Approximate 500 sequenced members.
  • Size ~ 400 residues but variable 12 or 14 spanners.

Reference:Stavri et al (2007)Bacterial efflux pump inhibitors from natural sources Journal of Antimicrobial Chemotherapy 59: 1247–1260






Resistance and Nodulation Division (RND) family

  • Found in prokaryotes (mainly gram negative bacteria) and Eukaryotes.
  • 12 membrane α helices, the functional transporter is trimer with a total 36 membrane spanning  α helices.
  • Well characterized members: NPC-1, Acr B, Mex B.
  • More than 16 sequenced members.
  • More than 1000 amino acid residues.

Reference:SAIER et al (1998) Evolutionary origins of multidrug and drug-specific efflux pumps in bacteria FASEB J. 12: 265–274.






Small Multidrug Resistance (SMR) family

  • Drug : H+ antiport.
  • Restricted to prokaryotic system.
  • 4 transmembrane α helices function as dimers the minimal functional unit is a bundle of eight α helices.
  • Mainly responsible for extrusion of hydrophobic cationic molecules including antibiotics.

Reference:Higgins (2007) Multiple molecular mechanisms for multidrug resistance transporters nature. 446: 749-757.





Multidrug and Toxic Compound Extrusion (MATE) family

  • A new multidrug efflux pump family.
  • Drug driven by the exchange of either H+ or Na+.
  • 12 putative α helices.
  • Responsible for removal of multiple structural chemotype.

Reference:.Stavri et al (2007)Bacterial efflux pump inhibitors from natural sources Journal of Antimicrobial Chemotherapy 59: 1247–1260.