Thermodynamic secrets of multidrug resistance: A new take on transport mechanisms of secondary active antiporters

Protein Sci. 2018 Mar;27(3):595-613. doi: 10.1002/pro.3355. Epub 2017 Dec 15.

Abstract

Multidrug resistance (MDR) presents a growing challenge to global public health. Drug extrusion transporters play a critical part in MDR; thus, their mechanisms of substrate recognition are being studied in great detail. In this work, we review common structural features of key transporters involved in MDR. Based on our membrane potential-driving hypothesis, we propose a general energy-coupling mechanism for secondary-active antiporters. This putative mechanism provides a common framework for understanding poly-specificity of most-if not all-MDR transporters.

Keywords: energy coupling; exporters; membrane potential; multidrug resistance; titratable residue.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antiporters / chemistry
  • Bacteria / metabolism*
  • Bacterial Proteins / chemistry
  • Biological Transport
  • Drug Resistance, Multiple*
  • Humans
  • Membrane Transport Proteins / chemistry*
  • Models, Molecular
  • Thermodynamics

Substances

  • Antiporters
  • Bacterial Proteins
  • Membrane Transport Proteins

Associated data

  • PDB/4ZOW
  • PDB/3W4T
  • PDB/3B5D
  • PDB/4DX5
  • PDB/3G5U
  • PDB/4LZ6
  • PDB/3MKT
  • PDB/2HYD
  • PDB/3W9H