Document Type

Journal Article

Publication Title

Computational and Structural Biotechnology Journal

Volume

19

First Page

691

Last Page

704

Publisher

Elsevier

School

School of Medical and Health Sciences

RAS ID

32734

Funders

Edith Cowan University Curtin University UTS Chancellor's Postdoctoral Research Fellowship Australian Government Government of Western Australia

Comments

Tangella, L. P., Arooj, M., Deplazes, E., Gray, E. S., & Mancera, R. L. (2021). Identification and characterisation of putative drug binding sites in human ATP-binding cassette B5 (ABCB5) transporter. Computational and Structural Biotechnology Journal, 19, 691-704. https://doi.org/10.1016/j.csbj.2020.12.042

Abstract

© 2020 The Author(s) The human ATP-binding cassette B5 (ABCB5) transporter, a member of the ABC transporter superfamily, is linked to chemoresistance in tumour cells by drug effluxion. However, little is known about its structure and drug-binding sites. In this study, we generated an atomistic model of the full-length human ABCB5 transporter with the highest quality using the X-ray crystal structure of mouse ABCB1 (Pgp1), a close homologue of ABCB5 and a well-studied member of the ABC family. Molecular dynamics simulations were used to validate the atomistic model of ABCB5 and characterise its structural properties in model cell membranes. Molecular docking simulations of known ABCB5 substrates such as taxanes, anthracyclines, camptothecin and etoposide were then used to identify at least three putative binding sites for chemotherapeutic drugs transported by ABCB5. The location of these three binding sites is predicted to overlap with the corresponding binding sites in Pgp1. These findings will serve as the basis for future in vitro studies to validate the nature of the identified substrate-binding sites in the full-length ABCB5 transporter.

DOI

10.1016/j.csbj.2020.12.042

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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