Switch Loop Flexibility Affects Substrate Transport of the AcrB Efflux Pump.
J Mol Biol
; 429(24): 3863-3874, 2017 12 08.
Article
en En
| MEDLINE
| ID: mdl-28987732
ABSTRACT
The functionally important switch loop of the trimeric multidrug transporter AcrB separates the access and deep drug binding pockets in every protomer. This loop, comprising 11-amino-acid residues, has been shown to be crucial for substrate transport, as drugs have to travel past the loop to reach the deep binding pocket and from there are transported outside the cell via the connected AcrA and TolC channels. It contains four symmetrically arranged glycine residues suggesting that flexibility is a key feature for pump activity. Upon combinatorial substitution of these glycine residues to proline, functional and structural asymmetry was observed. Proline substitutions on the PC1-proximal side completely abolished transport and reduced backbone flexibility of the switch loop, which adopted a conformation restricting the pathway toward the deep binding pocket. Two phenylalanine residues located adjacent to the substitution sensitive glycine residues play a role in blocking the pathway upon rigidification of the loop, since the removal of the phenyl rings from the rigid loop restores drug transport activity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Conformación Proteica
/
Proteínas de Escherichia coli
/
Proteínas Asociadas a Resistencia a Múltiples Medicamentos
/
Escherichia coli
/
Antibacterianos
Idioma:
En
Revista:
J Mol Biol
Año:
2017
Tipo del documento:
Article
País de afiliación:
Alemania