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Switch-loop flexibility affects transport of large drugs by the promiscuous AcrB multidrug efflux transporter.

ABSTRACT: Multidrug efflux transporters recognize a variety of structurally unrelated compounds for which the molecular basis is poorly understood. For the resistance nodulation and cell division (RND) inner membrane component AcrB of the AcrAB-TolC multidrug efflux system from Escherichia coli, drug binding occurs at the access and deep binding pockets. These two binding areas are separated by an 11-amino-acid-residue-containing switch loop whose conformational flexibility is speculated to be essential for drug binding and transport. A G616N substitution in the switch loop has a distinct and local effect on the orientation of the loop and on the ability to transport larger drugs. Here, we report a distinct phenotypical pattern of drug recognition and transport for the G616N variant, indicating that drug substrates with minimal projection areas of >70 Å(2) are less well transported than other substrates.

SUBMITTER: Cha HJ

PROVIDER: S-EPMC4136034 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Switch-loop flexibility affects transport of large drugs by the promiscuous AcrB multidrug efflux transporter.

Cha Hi-jea HJ Müller Reinke T RT Pos Klaas M KM

Antimicrobial agents and chemotherapy 20140609 8

Multidrug efflux transporters recognize a variety of structurally unrelated compounds for which the molecular basis is poorly understood. For the resistance nodulation and cell division (RND) inner membrane component AcrB of the AcrAB-TolC multidrug efflux system from Escherichia coli, drug binding occurs at the access and deep binding pockets. These two binding areas are separated by an 11-amino-acid-residue-containing switch loop whose conformational flexibility is speculated to be essential f ...[more]

PMID: 24914123

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Transport of drugs by the multidrug transporter AcrB involves an access and a deep binding pocket that are separated by a switch-loop.

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