Theoretical insights on helix repacking as the origin of P-glycoprotein promiscuity

• Published in: Scientific reports Vol. 10; no. 1; p. 9823
• Main Authors: Bonito, Cátia A, Ferreira, Ricardo J, Ferreira, Maria-José U, Gillet, Jean-Pierre, Cordeiro, M Natália D S, Dos Santos, Daniel J V A
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 17.06.2020; Nature Publishing Group UK
• Subjects: Adenosine triphosphatase; ATP Binding Cassette Transporter, Subfamily B, Member 1 - chemistry; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism; Binding Sites; Conformation; Glycoproteins; Homology; Humans; Interfaces; Lipid bilayers; Molecular Dynamics Simulation; Multidrug resistance; Mutation; P-Glycoprotein; Polarity; Protein Conformation, alpha-Helical; Protein Domains; Substrate Specificity; Transmembrane domains; Tumor cells

P-glycoprotein (P-gp, ABCB1) overexpression is, currently, one of the most important multidrug resistance (MDR) mechanisms in tumor cells. Thus, modulating drug efflux by P-gp has become one of the most promising approaches to overcome MDR in cancer. Yet, more insights on the molecular basis of drug...