Asymmetric protonation of EmrE

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Asymmetric protonation of EmrE.

The small multidrug resistance transporter EmrE is a homodimer that uses energy provided by the proton motive force to drive the efflux of drug substrates. The pKa values of its "active-site" residues--glutamate 14 (Glu14) from each subunit--must be poised around physiological pH values to efficiently couple proton import to drug export in vivo. To assess the protonation of EmrE, pH titrations ...

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Protonation-dependent conformational dynamics of the multidrug transporter EmrE.

The small multidrug transporter from Escherichia coli, EmrE, couples the energetically uphill extrusion of hydrophobic cations out of the cell to the transport of two protons down their electrochemical gradient. Although principal mechanistic elements of proton/substrate antiport have been described, the structural record is limited to the conformation of the substrate-bound state, which has be...

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Protonation of a Glutamate Residue Modulates the Dynamics of the Drug Transporter EmrE

Secondary active transport proteins play a central role in conferring bacterial multidrug resistance. In this work, we investigated the proton-coupled transport mechanism for the Escherichia coli drug efflux pump EmrE using NMR spectroscopy. Our results show that the global conformational motions necessary for transport are modulated in an allosteric fashion by the protonation state of a membra...

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Synthesis of Enantioenriched Indolines by a Conjugate Addition/Asymmetric Protonation/Aza-Prins Cascade Reaction.

A conjugate addition/asymmetric protonation/aza-Prins cascade reaction has been developed for the enantioselective synthesis of fused polycyclic indolines. A catalyst system generated from ZrCl4 and 3,3'-dibromo-BINOL enables the synthesis of a range of polycyclic indolines in good yields and with high enantioselectivity. A key finding is the use of TMSCl and 2,6-dibromophenol as a stoichiometr...

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ژورنال

عنوان ژورنال: Journal of General Physiology

سال: 2015

ISSN: 1540-7748,0022-1295

DOI: 10.1085/jgp.201511404