Conformational changes in the nucleotide-binding domains of P-glycoprotein induced by ATP hydrolysis.
FEBS Lett
; 595(6): 735-749, 2021 03.
Article
em En
| MEDLINE
| ID: mdl-33159693
ABSTRACT
P-glycoprotein (Pgp) is a member of the ABC transporter superfamily with high physiological importance. Pgp nucleotide-binding domains (NBDs) drive the transport cycle through ATP binding and hydrolysis. We use molecular dynamics simulations to investigate the ATP hydrolysis-induced conformational changes in NBDs. Five systems, including all possible ATP/ADP combinations in the NBDs and the APO system, are simulated. ATP/ADP exchange induces conformational changes mostly within the conserved signature motif of the NBDs, resulting in relative orientational changes in the NBDs. Nucleotide removal leads to additional orientational changes in the NBDs, allowing their dissociation. Furthermore, we capture putative hydrolysis-competent configurations in which the conserved glutamate in the Walker-B motif acts as a catalytic base capturing a water molecule likely initiating ATP hydrolysis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trifosfato de Adenosina
/
Simulação de Dinâmica Molecular
Limite:
Humans
Idioma:
En
Revista:
FEBS Lett
Ano de publicação:
2021
Tipo de documento:
Article