ArticleProceedings of the National Academy of Sciences of the United States of America2013
Structures of P-glycoprotein reveal its conformational flexibility and an epitope on the nucleotide-binding domain.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 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
124 citing papers in PubMed, 255 citations in OpenAlex.
- Genomic Deletion of P-Glycoprotein from Gliomas Via the Focused Ultrasound-Delivery of a Duplex CRISPR Cas9 Ribonucleoprotein System.Cell biomaterials · 2026Article
- N-benzylbenzamide derivative (SBM685) as a novel MDR1 inhibitor for overcoming 5 fluorouracil resistance in gastric cancer through computational and in vitro analysis.Discover oncology · 2026Article
- Developing Potent Therapeutics for Liver Cancer Chemoresistance via an RNA Nanotech and Series-Circuit-Christmas-Bulb Mechanism Targeting ABC Transporters.Molecular pharmaceutics · 2026Review
- Visualizing the Functional Dynamics of P-Glycoprotein and Its Modulation by Elacridar via High-Speed Atomic Force Microscopy.International journal of molecular sciences · 2025Article
- The canine blood-brain barrier in health and disease: focus on brain protection.The veterinary quarterly · 2025Review
- Simulation and Machine Learning Assessment of P-Glycoprotein Pharmacology in the Blood-Brain Barrier: Inhibition and Substrate Transport.International journal of molecular sciences · 2025Article
- Cryo-EM Structures of Apo and DDT-Bound P-Glycoprotein in Yellowfin Tuna.Environmental science & technology · 2025Article
- Mapping the Role of P-gp in Multidrug Resistance: Insights from Recent Structural Studies.International journal of molecular sciences · 2025Review
- Cryo-EM of human P-glycoprotein reveals an intermediate occluded conformation during active drug transport.Nature communications · 2025Article
- Article
- Review
- ATP-Binding Cassette and Solute Carrier Transporters: Understanding Their Mechanisms and Drug Modulation Through Structural and Modeling Approaches.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Structural View of Cryo-Electron Microscopy-Determined ATP-Binding Cassette Transporters in Human Multidrug Resistance.Biomolecules · 2024Review
- Mass Spectrometry Investigation of Some ATP-Binding Cassette (ABC) Proteins.Medicina (Kaunas, Lithuania) · 2024Review
- 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
- Advantages and potential limitations of applying AFM kymograph analysis to pharmaceutically relevant membrane proteins in lipid bilayers.Scientific reports · 2023Article
- αCharges: partial atomic charges for AlphaFold structures in high quality.Nucleic acids research · 2023Article
- Residues from Homologous Transmembrane Helices 4 and 10 Are Critical for P-Glycoprotein (ABCB1)-Mediated Drug Transport.Cancers · 2023Article
64 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
16 authors at 6 institutions in 4 countries.
Funding
Abstract
P-glycoprotein (P-gp) is one of the best-known mediators of drug efflux-based multidrug resistance in many cancers. This validated therapeutic target is a prototypic, plasma membrane resident ATP-Binding Cassette transporter that pumps xenobiotic compounds out of cells. The large, polyspecific drug-binding pocket of P-gp recognizes a variety of structurally unrelated compounds. The transport of these drugs across the membrane is coincident with changes in the size and shape of this pocket during the course of the transport cycle. Here, we present the crystal structures of three inward-facing conformations of mouse P-gp derived from two different crystal forms. One structure has a nanobody bound to the C-terminal side of the first nucleotide-binding domain. This nanobody strongly inhibits the ATP hydrolysis activity of mouse P-gp by hindering the formation of a dimeric complex between the ATP-binding domains, which is essential for nucleotide hydrolysis. Together, these inward-facing conformational snapshots of P-gp demonstrate a range of flexibility exhibited by this transporter, which is likely an essential feature for the binding and transport of large, diverse substrates. The nanobody-bound structure also reveals a unique epitope on P-gp.
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.