ArticlePharmacology research & perspectives2020
Active transport of rhodamine 123 by the human multidrug transporter P-glycoprotein involves two independent outer gates.
Article in Pharmacology research & perspectives, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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
11 citing papers in PubMed, 13 citations in OpenAlex.
- Derivation of functional retinal endothelial cells from human pluripotent stem cells for therapeutics and modelling.Nature biomedical engineering · 2026Article
- Rational design of pyrazole-oxime hybrids as dual-targeting agents for glioma and breast cancer brain metastasis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Pamamycin Disrupts the Cell Envelope and Mitochondrial Potential to InhibitFoods (Basel, Switzerland) · 2026Article
- Modelling the maternal-fetal interface: An in vitro approach to investigate nutrient and drug transport across the human placenta.Journal of cellular and molecular medicine · 2024Article
- Coupling the role of lipids to the conformational dynamics of the ABC transporter P-glycoprotein.Biophysical journal · 2024Article
- Structural insight into binding site access and ligand recognition by human ABCB1.bioRxiv : the preprint server for biology · 2024Article
- The Anthraquinone Derivative C2 Enhances Oxaliplatin-Induced Cell Death and Triggers Autophagy via the PI3K/AKT/mTOR Pathway.International journal of molecular sciences · 2024Article
- Bidirectional ATP-driven transport of cobalamin by the mycobacterial ABC transporter BacA.Nature communications · 2024Article
- Decrease of ABCB1 protein expression and increase of GExperimental and therapeutic medicine · 2021Article
- The role of the degenerate nucleotide binding site in type I ABC exporters.FEBS letters · 2020Review
- Active transport of rhodamine 123 by the human multidrug transporter P-glycoprotein involves two independent outer gates.Pharmacology research & perspectives · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Human P-glycoprotein (P-gp) is a multispecific drug-efflux transporter, which plays an important role in drug resistance and drug disposition. Recent cryo-electron microscopy structures confirmed its rotationally symmetric architecture, which allows dual interaction with ATP and substrates. We here report the existence of two distinct, symmetry-related outer gates. Experiments were aided by availability of the X-ray structure of a homodimeric eukaryotic homolog of P-gp from red alga (CmABCB1), which defined the role of an apical tyrosine residue (Y358) in outer gate formation. We mutated analogous tyrosine residues in each half of the human full-length transporter (Y310, Y953) to alanine. These mutants were introduced in engineered transporters which bind rhodamine 123 in one of two symmetry-related binding modes only. Outer gate dysfunction was detected by a loss of active transport characteristics, while these mutants retained the ability for outward downhill transport. Our data demonstrate that symmetric tyrosine residues Y310 and Y953 are involved in formation of two distinct symmetry-related outer gates, which operate contingent on the rhodamine 123 binding mode. Hence, the rotationally symmetric architecture of P-gp, which determines duality in ATP binding and rhodamine 123 interaction, also forms the basis for the existence of two independently operating outer gates.
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.