ArticleThe Journal of biological chemistry2013
On the origin of large flexibility of P-glycoprotein in the inward-facing state.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
69 citing papers in PubMed, 132 citations in OpenAlex.
- Integrated machine learning and molecular dynamics framework for predicting and elucidating ABCB1 allocrite interactions.Briefings in bioinformatics · 2026Article
- Molecular characterisation of the trafficking rescue of defective ABCB4 variants by roscovitine analogues.Scientific reports · 2026Article
- Visualizing the Functional Dynamics of P-Glycoprotein and Its Modulation by Elacridar via High-Speed Atomic Force Microscopy.International journal of molecular sciences · 2025Article
- Drug-bound outward-facing conformation of a heterodimeric ABC exporter suggests a putative mechanism of drug translocation.Nature communications · 2025Article
- Membrane-dependent dynamics and dual translocation mechanisms of ABCB4: Insights from molecular dynamics simulations.Computational and structural biotechnology journal · 2025Article
- Coupling the role of lipids to the conformational dynamics of the ABC transporter P-glycoprotein.Biophysical journal · 2024Article
- Mass Spectrometry Investigation of Some ATP-Binding Cassette (ABC) Proteins.Medicina (Kaunas, Lithuania) · 2024Review
- The transport activity of the multidrug ABC transporter BmrA does not require a wide separation of the nucleotide-binding domains.The Journal of biological chemistry · 2024Article
- Membrane-assisted tariquidar access and binding mechanisms of human ATP-binding cassette transporter P-glycoprotein.Frontiers in molecular biosciences · 2024Article
- Modeling Substrate Entry into the P-Glycoprotein Efflux Pump at the Blood-Brain Barrier.Journal of medicinal chemistry · 2023Article
- How Cryo-EM Has Expanded Our Understanding of Membrane Transporters.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- In Silico and In Vitro Identification of P-Glycoprotein Inhibitors from a Library of 375 Phytochemicals.International journal of molecular sciences · 2023Article
- The Alternating Access Mechanism in Mammalian Multidrug Resistance Transporters and Their Bacterial Homologs.Membranes · 2023Article
- On the interplay between lipids and asymmetric dynamics of an NBS degenerate ABC transporter.Communications biology · 2023Article
- Interaction of a Homologous Series of Amphiphiles with P-glycoprotein in a Membrane Environment-Contributions of Polar and Non-Polar Interactions.Pharmaceutics · 2023Article
- Differential dynamics and direct interaction of bound ligands with lipids in multidrug transporter ABCG2.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Long Range Communication between the Drug-Binding Sites and Nucleotide Binding Domains of the Efflux Transporter ABCB1.Biochemistry · 2022Article
- Extended-ensemble docking to probe dynamic variation of ligand binding sites during large-scale structural changes of proteins.Chemical science · 2022Article
- Substrate-bound and substrate-free outward-facing structures of a multidrug ABC exporter.Science advances · 2022Article
- Active participation of membrane lipids in inhibition of multidrug transporter P-glycoprotein.Chemical science · 2021Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
P-glycoprotein (Pgp) is one of the most biomedically relevant transporters in the ATP binding cassette (ABC) superfamily due to its involvement in developing multidrug resistance in cancer cells. Employing molecular dynamics simulations and double electron-electron resonance spectroscopy, we have investigated the structural dynamics of membrane-bound Pgp in the inward-facing state and found that Pgp adopts an unexpectedly wide range of conformations, highlighted by the degree of separation between the two nucleotide-binding domains (NBDs). The distance between the two NBDs in the equilibrium simulations covers a range of at least 20 Å, including, both, more open and more closed NBD configurations than the crystal structure. The double electron-electron resonance measurements on spin-labeled Pgp mutants also show wide distributions covering both longer and shorter distances than those observed in the crystal structure. Based on structural and sequence analyses, we propose that the transmembrane domains of Pgp might be more flexible than other structurally known ABC exporters. The structural flexibility of Pgp demonstrated here is not only in close agreement with, but also helps rationalize, the reported high NBD fluctuations in several ABC exporters and possibly represents a fundamental difference in the transport mechanism between ABC exporters and ABC importers. In addition, during the simulations we have captured partial entrance of a lipid molecule from the bilayer into the lumen of Pgp, reaching the putative drug binding site. The location of the protruding lipid suggests a putative pathway for direct drug recruitment from the membrane.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.