ArticleBMC structural biology2018
Novel features in the structure of P-glycoprotein (ABCB1) in the post-hydrolytic state as determined at 7.9 Å resolution.
Article in BMC structural biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- Mapping the Role of P-gp in Multidrug Resistance: Insights from Recent Structural Studies.International journal of molecular sciences · 2025Review
- Nucleotide asymmetry and flexible linker dynamics modulate drug efflux cycle of P-glycoprotein, A computational study.Computational and structural biotechnology journal · 2025Article
- Coupling the role of lipids to the conformational dynamics of the ABC transporter P-glycoprotein.Biophysical journal · 2024Article
- The Alternating Access Mechanism in Mammalian Multidrug Resistance Transporters and Their Bacterial Homologs.Membranes · 2023Article
- The Interaction between Four Polymorphisms and Haplotype ofJournal of oncology · 2023Article
- P-glycoprotein: new insights into structure, physiological function, regulation and alterations in disease.Heliyon · 2022Review
- Long Range Communication between the Drug-Binding Sites and Nucleotide Binding Domains of the Efflux Transporter ABCB1.Biochemistry · 2022Article
- Structure of ABCB1/P-Glycoprotein in the Presence of the CFTR Potentiator Ivacaftor.Membranes · 2021Article
- Structure of Ycf1p reveals the transmembrane domain TMD0 and the regulatory region of ABCC transporters.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The crystal structure of the CmABCB1 G132V mutant, which favors the outward-facing state, reveals the mechanism of the pivotal joint between TM1 and TM3.Protein science : a publication of the Protein Society · 2021Article
- Multidrug Resistance in Mammals and Fungi-From MDR to PDR: A Rocky Road from Atomic Structures to Transport Mechanisms.International journal of molecular sciences · 2021Review
- The Bile Salt Export Pump: Molecular Structure, Study Models and Small-Molecule Drugs for the Treatment of Inherited BSEP Deficiencies.International journal of molecular sciences · 2021Review
- The Structure and Mechanism of Drug Transporters.Methods in molecular biology (Clifton, N.J.) · 2021Article
- 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
- The role of the degenerate nucleotide binding site in type I ABC exporters.FEBS letters · 2020Review
- Theoretical insights on helix repacking as the origin of P-glycoprotein promiscuity.Scientific reports · 2020Article
- Linker Domains: Why ABC Transporters 'Live in Fragments no Longer'.Trends in biochemical sciences · 2020Review
- Perplexing Role of P-Glycoprotein in Tumor Microenvironment.Frontiers in oncology · 2020Review
- Functional Expression of Multidrug Resistance Protein 4 MRP4/ABCC4.SLAS discovery : advancing life sciences R & D · 2019Article
- Dynamics of ABC Transporter P-glycoprotein in Three Conformational States.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundP-glycoprotein (ABCB1) is an ATP-binding cassette transporter that plays an important role in the clearance of drugs and xenobiotics and is associated with multi-drug resistance in cancer. Although several P-glycoprotein structures are available, these are either at low resolution, or represent mutated and/or quiescent states of the protein.
resultsIn the post-hydrolytic state the structure of the wild-type protein has been resolved at about 8 Å resolution. The cytosolic nucleotide-binding domains (NBDs) are separated but ADP remains bound, especially at the first NBD. Gaps in the transmembrane domains (TMDs) that connect to an inner hydrophilic cavity are filled by density emerging from the annular detergent micelle. The NBD-TMD linker is partly resolved, being located between the NBDs and close to the Signature regions involved in cooperative NBD dimerization. This, and the gap-filling detergent suggest steric impediment to NBD dimerization in the post-hydrolytic state. Two central regions of density lie in two predicted drug-binding sites, implying that the protein may adventitiously bind hydrophobic substances even in the post-hydrolytic state. The previously unresolved N-terminal extension was observed, and the data suggests these 30 residues interact with the headgroup region of the lipid bilayer.
conclusionThe structural data imply that (i) a low basal ATPase activity is ensured by steric blockers of NBD dimerization and (ii) allocrite access to the central cavity may be structurally linked to NBD dimerization, giving insights into the mechanism of drug-stimulation of P-glycoprotein activity.
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