Work

Does the ATP‐bound EQ mutant reflect the pre‐ or post‐ATP hydrolysis state in the catalytic cycle of human P‐glycoprotein (ABCB1)?

Year: 2021

Type: article

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.

Source: FEBS Letters

DOI: 10.1002/1873-3468.14054

Authors: Sabrina Lusvarghi, Stewart R. Durell, Suresh V. Ambudkar

Institutions: National Institutes of Health, National Cancer Institute, Center for Cancer Research

Language: English

Topic: Drug Transport and Resistance Mechanisms

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Institutes of Health