Does the ATP-bound EQ mutant reflect the pre- or post-ATP hydrolysis state in the catalytic cycle of human P-glycoprotein (ABCB1)?
FEBS Lett
; 595(6): 750-762, 2021 03.
Article
em En
| MEDLINE
| ID: mdl-33547668
ABSTRACT
P-glycoprotein (P-gp, ABCB1) is an ABC transporter associated with the development of multidrug resistance to chemotherapy. During its catalytic cycle, P-gp undergoes significant conformational changes. Recently, atomic structures of some of these conformations have been resolved using cryo-electron microscopy. The ATP hydrolysis-defective mutant of the catalytic glutamate residue of the Walker B motif (E556Q/E1201Q) has been used to determine the structure of the ATP-bound inward-closed conformation of P-gp. Here, we show that this mutant does not appear to undergo the same steps as wild-type P-gp. We discuss conformational differences in the EQ mutant that may lead to a better understanding of the catalytic cycle of P-gp and propose that additional structural studies with wild-type P-gp are required.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trifosfato de Adenosina
/
Mutação de Sentido Incorreto
Limite:
Humans
Idioma:
En
Revista:
FEBS Lett
Ano de publicação:
2021
Tipo de documento:
Article