Structure-function relationships in ABCG2: Insights from molecular dynamics simulations and molecular docking studies

Ricardo J. Ferreira, Cátia A. Bonito, M. Natália D.S. Cordeiro, Maria José U. Ferreira, Daniel J.V.A. Dos Santos

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

Abstract

Efflux pumps of the ATP-binding cassette transporters superfamily (ABC transporters) are frequently involved in the multidrug-resistance (MDR) phenomenon in cancer cells. Herein, we describe a new atomistic model for the MDR-related ABCG2 efflux pump, also named breast cancer resistance protein (BCRP), based on the recently published crystallographic structure of the ABCG5/G8 heterodimer sterol transporter, a member of the ABCG family involved in cholesterol homeostasis. By means of molecular dynamics simulations and molecular docking, a far-reaching characterization of the ABCG2 homodimer was obtained. The role of important residues and motifs in the structural stability of the transporter was comprehensively studied and was found to be in good agreement with the available experimental data published in literature. Moreover, structural motifs potentially involved in signal transmission were identified, along with two symmetrical drug-binding sites that are herein described for the first time, in a rational attempt to better understand how drug binding and recognition occurs in ABCG2 homodimeric transporters.

Original languageEnglish
Article number15534
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 The Author(s).

Fingerprint

Dive into the research topics of 'Structure-function relationships in ABCG2: Insights from molecular dynamics simulations and molecular docking studies'. Together they form a unique fingerprint.

Cite this