ArticlePloS one2016
Jump into a New Fold-A Homology Based Model for the ABCG2/BCRP Multidrug Transporter.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
- ABCG2 Transporter: From Structure to Function-Current Insights and Open Questions.International journal of molecular sciences · 2025Review
- A key residue of the extracellular gate provides quality control contributing to ABCG substrate specificity.Nature communications · 2025Article
- Revisiting the Role of the Leucine Plug/Valve in the Human ABCG2 Multidrug Transporter.International journal of molecular sciences · 2025Article
- ATP-Binding Cassette and Solute Carrier Transporters: Understanding Their Mechanisms and Drug Modulation Through Structural and Modeling Approaches.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Identification of a muropeptide precursor transporter from gut microbiota and its role in preventing intestinal inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A Structure-Based View on ABC-Transporter Linked to Multidrug Resistance.Molecules (Basel, Switzerland) · 2023Review
- Ins and outs of AlphaFold2 transmembrane protein structure predictions.Cellular and molecular life sciences : CMLS · 2022Article
- ABCG2/BCRP transport mechanism revealed through kinetically excited targeted molecular dynamics simulations.Computational and structural biotechnology journal · 2022Article
- Tetrahydroquinoline/4,5-Dihydroisoxazole Molecular Hybrids as Inhibitors of Breast Cancer Resistance Protein (BCRP/ABCG2).ChemMedChem · 2021Article
- The Role of ABCG2 in the Pathogenesis of Primary Hyperuricemia and Gout-An Update.International journal of molecular sciences · 2021Review
- Structure-Based Discovery of ABCG2 Inhibitors: A Homology Protein-Based Pharmacophore Modeling and Molecular Docking Approach.Molecules (Basel, Switzerland) · 2021Article
- Cryo-EM structure of ABCG5/G8 in complex with modulating antibodies.Communications biology · 2021Article
- Analysis of Sequence Divergence in Mammalian ABCGs Predicts a Structural Network of Residues That Underlies Functional Divergence.International journal of molecular sciences · 2021Article
- Medically Important Alterations in Transport Function and Trafficking of ABCG2.International journal of molecular sciences · 2021Review
- The transport pathway in the ABCG2 protein and its regulation revealed by molecular dynamics simulations.Cellular and molecular life sciences : CMLS · 2021Article
- The first intracellular loop is essential for the catalytic cycle of the human ABCG2 multidrug resistance transporter.FEBS letters · 2020Article
- Review
- Binding Site Interactions of Modulators of Breast Cancer Resistance Protein, Multidrug Resistance-Associated Protein 2, and P-Glycoprotein Activity.Molecular pharmaceutics · 2020Article
- 3D structure of the transporter ABCG2-What's new?British journal of pharmacology · 2020Review
- Disruption of the Unique ABCG-Family NBD:NBD Interface Impacts Both Drug Transport and ATP Hydrolysis.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ABCG2/BCRP is a membrane protein, involved in xenobiotic and endobiotic transport in key pharmacological barriers and drug metabolizing organs, in the protection of stem cells, and in multidrug resistance of cancer. Pharmacogenetic studies implicated the role of ABCG2 in response to widely used medicines and anticancer agents, as well as in gout. Its Q141K variant exhibits decreased functional expression thus increased drug accumulation and decreased urate secretion. Still, there has been no reliable molecular model available for this protein, as the published structures of other ABC transporters could not be properly fitted to the ABCG2 topology and experimental data. The recently published high resolution structure of a close homologue, the ABCG5-ABCG8 heterodimer, revealed a new ABC transporter fold, unique for ABCG proteins. Here we present a structural model of the ABCG2 homodimer based on this fold and detail the experimental results supporting this model. In order to describe the effect of mutations on structure and dynamics, and characterize substrate recognition and cholesterol regulation we performed molecular dynamics simulations using full length ABCG2 protein embedded in a membrane bilayer and in silico docking simulations. Our results show that in the Q141K variant the introduced positive charge diminishes the interaction between the nucleotide binding and transmembrane domains and the R482G variation alters the orientation of transmembrane helices. Moreover, the R482 position, which plays a role the substrate specificity of the transporter, is located in one of the substrate binding pockets identified by the in silico docking calculations. In summary, the ABCG2 model and in silico simulations presented here may have significant impact on understanding drug distribution and toxicity, as well as drug development against cancer chemotherapy resistance or gout.
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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.