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J Biol Chem. 2014 Mar 7;289(10):6825-36. doi: 10.1074/jbc.M113.535328. Epub 2014 Jan 21.

Transported substrate determines exchange rate in the multidrug resistance transporter EmrE.

Author information

1
From the Department of Biochemistry and Molecular Biophysics, Washington University, St. Louis School of Medicine, St. Louis, Missouri 63110.

Abstract

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. 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.

KEYWORDS:

Membrane Transport; Multidrug Transporters; NMR; Protein Drug Interactions; Protein Dynamics

PMID:
24448799
PMCID:
PMC3945343
DOI:
10.1074/jbc.M113.535328
[Indexed for MEDLINE]
Free PMC Article

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