Insights into the ion-coupling mechanism in the MATE transporter NorM-VC

Alexander Krah (Lead / Corresponding author), Ulrich Zachariae

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)
298 Downloads (Pure)

Abstract

Bacteria have developed a variety of different mechanisms to defend themselves from compounds that are toxic to them, such as antibiotics. One of these defence mechanisms is the expulsion of drugs or other noxious compounds by multidrug efflux pumps. Multidrug and toxic compound extrusion (MATE) transporters are efflux pumps that extrude metabolic waste and a variety of antibiotics out of the cell, using an ion gradient as energy source. They function via an alternative-access mechanism. When ions bind in the outward facing conformation, a large conformational change to the inward facing conformation is induced, from which the ion is released and the extruded chemical compound is bound. NorM proteins, which are usually coupled to a Na+ gradient, are members of the MATE family. However, for NorM-VC from Vibrio cholerae, it has been shown that this MATE transporter is additionally coupled to protons. How H+ and Na+ binding are coupled mechanistically to enable drug antiport is not well understood. In this study, we use molecular dynamics simulations to illuminate the sequence of ion binding event that enable efflux. Understanding this antiport mechanism is important to support the development of novel compounds that specifically inhibit the functional cycle of NorM transporters.
Original languageEnglish
Article number045009
JournalPhysical Biology
Volume14
Early online date7 Feb 2017
DOIs
Publication statusPublished - 24 Jul 2017

Keywords

  • MATE transporter
  • MD simulations
  • antimicrobial resistance

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