ArticleThe Journal of biological chemistry2011
Conformational analysis of human ATP-binding cassette transporter ABCB1 in lipid nanodiscs and inhibition by the antibodies MRK16 and UIC2.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 71 citations in OpenAlex.
- Article
- Drug-Induced Conformational Dynamics of P-Glycoprotein Underlies the Transport of Camptothecin Analogs.International journal of molecular sciences · 2023Article
- Anti-nanodisc antibodies specifically capture nanodiscs and facilitate molecular interaction kinetics studies for membrane protein.Scientific reports · 2023Article
- Residues from Homologous Transmembrane Helices 4 and 10 Are Critical for P-Glycoprotein (ABCB1)-Mediated Drug Transport.Cancers · 2023Article
- In Vivo Reversal of P-Glycoprotein-Mediated Drug Resistance in a Breast Cancer Xenograft and in Leukemia Models Using a Novel, Potent, and Nontoxic Epicatechin EC31.International journal of molecular sciences · 2023Article
- Role of multidrug resistance-associated proteins in cancer therapeutics: past, present, and future perspectives.Environmental science and pollution research international · 2021Review
- Does the ATP-bound EQ mutant reflect the pre- or post-ATP hydrolysis state in the catalytic cycle of human P-glycoprotein (ABCB1)?FEBS letters · 2021Article
- Nanodiscs: A toolkit for membrane protein science.Protein science : a publication of the Protein Society · 2021Review
- The roles of the human ATP-binding cassette transporters P-glycoprotein and ABCG2 in multidrug resistance in cancer and at endogenous sites: future opportunities for structure-based drug design of inhibitors.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Disruption of small molecule transporter systems by Transporter-Interfering Chemicals (TICs).FEBS letters · 2020Review
- Reversing the direction of drug transport mediated by the human multidrug transporter P-glycoprotein.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Cryo-EM structures reveal distinct mechanisms of inhibition of the human multidrug transporter ABCB1.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The effects of anthracycline drugs on the conformational distribution of mouse P-glycoprotein explains their transport rate differences.Biochemical pharmacology · 2020Article
- Article
- Cancer Stem Cells as a Potential Target to Overcome Multidrug Resistance.Frontiers in oncology · 2020Review
- Large-scale purification of functional human P-glycoprotein (ABCB1).Protein expression and purification · 2019Article
- The conformation and dynamics of P-glycoprotein in a lipid bilayer investigated by atomic force microscopy.Biochemical pharmacology · 2018Article
- A Conformationally Gated Model of Methadone and Loperamide Transport by P-Glycoprotein.Journal of pharmaceutical sciences · 2018Article
- Structure of a zosuquidar and UIC2-bound human-mouse chimeric ABCB1.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Evidence for the critical role of transmembrane helices 1 and 7 in substrate transport by human P-glycoprotein (ABCB1).PloS one · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The human ATP-binding cassette (ABC) transporter, P-glycoprotein (P-gp; ABCB1), mediates the ATP-dependent efflux of a variety of drugs. As a result, P-gp plays a critical role in tumor cell drug resistance and the pharmacokinetic properties of most drugs. P-gp exhibits extraordinary substrate and inhibitor promiscuity, resulting in a wide range of possible drug-drug interactions. Inhibitory antibodies have long been considered as a possible strategy to modulate P-gp-dependent cancer cell drug resistance, and it is widely suggested that the antibodies MRK16 and UIC2 inhibit P-gp by capturing a single isoform and preventing flux through the catalytic cycle. Although the crystal structures of many bacterial whole transporters, as well as isolated nucleotide-binding domains, have been solved, high resolution structural data for mammalian ABC transporters are currently lacking. It has been extremely difficult to determine the detailed mechanism of transport of P-gp, in part because it is difficult to obtain purified protein in well defined lipid systems. Here we exploit surface plasmon resonance (SPR) to probe conformational changes associated with these intermediate states for P-gp in lipid bilayer nanodiscs. The results indicate that P-gp in nanodiscs undergoes functionally relevant ligand-dependent conformational changes and that previously described inhibitory antibodies bind to multiple nucleotide-bound states but not the ADP-VO(4)-trapped state, which mimics the post-hydrolysis state. The results also suggest that the substrate drug vinblastine is released at stages that precede or follow the post-hydrolysis ADP-PO(4)·P-gp complex.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.