Switch-loop flexibility affects transport of large drugs by the promiscuous AcrB multidrug efflux transporter.
Antimicrob Agents Chemother
; 58(8): 4767-72, 2014 Aug.
Article
em En
| MEDLINE
| ID: mdl-24914123
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Xenobióticos
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Substituição de Aminoácidos
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Proteínas de Escherichia coli
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Proteínas Associadas à Resistência a Múltiplos Medicamentos
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Escherichia coli
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Antibacterianos
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article