The pumping mechanism of the “drug pumping protein”: the cause of drug resistance is now clear – The molecular mechanism of the multidrug efflux transporter, or MdfA

October 01(Mon), 2018

The primary cause of a bacteria becoming drug-resistant is a protein that is called a multidrug efflux transporter that exists on the bacterial membrane pumping drugs out of the bacteria and making the drugs ineffective. There are many of these multidrug efflux transporters that are part of the MFS (Major Facilitator Superfamily) and exist on the bacteria, but the molecular mechanisms of how they identify drug molecules and pump them out of the bacteria are still unknown.

A collaborative research group consisting of the Institute of Materials Structure Science at the High Energy Accelerator Research Organization (KEK), the Institut für Biochemie & Biotechnologie at Martin Luther University of Halle-Wittenberg (Germany), the Graduate School of Medicine at Kyoto University, the Graduate School of Agricultural and Life Sciences at the University of Tokyo, and the Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and the Advanced Science Research Center at Okayama University conducted research on the efflux mechanism of MdfA, one of the MFS multidrug efflux transporters. The research used crystal structure analyses, transport activity experiments and a molecular dynamics simulation method to reveal details on the mechanism of the above drug molecule transportations.

The knowledge gained through this research gave a deeper understanding of the drug molecule efflux. In the future, it is expected to contribute to the development of a drug that fights against drug-resistant bacteria by controlling the activities of drug efflux transporters.

Article Information

DOI: 10.1038/s41467-018-06306-x.
Journal: Nature Communications
Authors: Kumar Nagarathinam, Yoshiko Nakada-Nakura, Christoph Parthier, Tohru Terada, Narinobu Juge, Frank Jaenecke, Kehong Liu, Yunhon Hotta, Takaaki Miyaji, Hiroshi Omote, So Iwata, Norimichi Nomura, Milton T. Stubbs and Mikio Tanabe
Title: Outward open conformation of a Major Facilitator Superfamily multidrug/H+ antiporter provides insights into switching mechanism
Year of Publication: 2018

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