News Column

Studies in the Area of Drug Resistance Reported from Washington University

June 18, 2014

By a News Reporter-Staff News Editor at Biotech Week -- Investigators discuss new findings in Drugs and Therapies. According to news reporting originating in St. Louis, Missouri, by NewsRx journalists, research stated, "EmrE transports a broad range of compounds. EmrE converts between open-in and open-out states with rates that vary over 3 orders of magnitude, depending on substrate."

The news reporters obtained a quote from the research from Washington University, "Substrate affects both ground-state and transition-state energies for conformational exchange, emphasizing the coupling between substrate binding and transport. Drug identity determines its own rate of transport by EmrE. EmrE, a small multidrug resistance transporter, serves as an ideal model to study coupling between multidrug recognition and protein function. EmrE has a single small binding pocket that must accommodate the full range of diverse substrates recognized by this transporter. We have studied a series of tetrahedral compounds, as well as several planar substrates, to examine multidrug recognition and transport by EmrE. Here we show that even within this limited series, the rate of interconversion between the inward- and outward-facing states of EmrE varies over 3 orders of magnitude. Thus, the identity of the bound substrate controls the rate of this critical step in the transport process. The binding affinity also varies over a similar range and is correlated with substrate hydrophobicity within the tetrahedral substrate series."

According to the news reporters, the research concluded: "Substrate identity influences both the ground-state and transition-state energies for the conformational exchange process, highlighting the coupling between substrate binding and transport required for alternating access antiport."

For more information on this research see: Transported Substrate Determines Exchange Rate in the Multidrug Resistance Transporter EmrE. Journal of Biological Chemistry, 2014;289(10):6825-6836. Journal of Biological Chemistry can be contacted at: Amer Soc Biochemistry Molecular Biology Inc, 9650 Rockville Pike, Bethesda, MD 20814-3996, USA. (American Society for Biochemistry and Molecular Biology -; Journal of Biological Chemistry -

Our news correspondents report that additional information may be obtained by contacting E.A. Morrison, Washington University, St Louis Sch Med, Dept. of Biochem & Mol Biophys, St Louis, MO 63110, United States (see also Drugs and Therapies).

Keywords for this news article include: Missouri, St. Louis, United States, Drug Resistance, Drugs and Therapies, North and Central America

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Source: Biotech Week

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