ArticleScience (New York, N.Y.)2021
Distinct allosteric mechanisms of first-generation MsbA inhibitors.
Article in Science (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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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
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Protein Spatial Structure Meets Artificial Intelligence: Revolutionizing Drug Synergy-Antagonism in Precision Medicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Pooled it
- Structure and druggable conformation of the homodimeric lipoprotein transporter of Acinetobacter baumannii.Nature communications · 2026Article
- Bacterial cell envelope-targeting antibiotics.Nature reviews. Microbiology · 2026Review
- Molecular Basis for the Activation ofJournal of the American Chemical Society · 2025Article
- Lipopolysaccharide: Recent Advances in Its Biosynthesis and Controlling Cell Envelope Homeostasis.International journal of molecular sciences · 2025Article
- Conformational cycle and small-molecule inhibition mechanism of a plant ABCB transporter in lipid membranes.Science advances · 2025Article
- Inhibiting Lipopolysaccharide Biogenesis: The More You Know the Further You Go.Annual review of biochemistry · 2025Review
- Conformational equilibrium of an ABC transporter analyzed by luminescence resonance energy transfer.Biophysical journal · 2025Article
- Integrated whole-exome and bulk transcriptome sequencing delineates the dynamic evolution from preneoplasia to invasive lung adenocarcinoma featured with ground-glass nodules.Cancer medicine · 2024Article
- The inactivation ofiScience · 2024Article
- Cerastecins inhibit membrane lipooligosaccharide transport in drug-resistant Acinetobacter baumannii.Nature microbiology · 2024Article
- A three-level regulatory mechanism of the aldo-keto reductase subfamily AKR12D.Nature communications · 2024Article
- Probing the functional hotspots inside protein hydrophobic pockets byChemical science · 2024Article
- Probing the allosteric NBD-TMD crosstalk in the ABC transporter MsbA by solid-state NMR.Communications biology · 2024Article
- Chemical genetic approaches for the discovery of bacterial cell wall inhibitors.RSC medicinal chemistry · 2023Review
- Asymmetric conformations and lipid interactions shape the ATP-coupled cycle of a heterodimeric ABC transporter.Nature communications · 2023Article
- The structure of phosphatidylinositol remodeling MBOAT7 reveals its catalytic mechanism and enables inhibitor identification.Nature communications · 2023Article
- Biosensor for Multimodal Characterization of an Essential ABC Transporter for Next-Generation Antibiotic Research.ACS applied materials & interfaces · 2023Article
- Structural basis for lipid and copper regulation of the ABC transporter MsbA.Nature communications · 2022Article
- The ABC transporter MsbA adopts the wide inward-open conformation inScience advances · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
ATP-binding cassette (ABC) transporters couple adenosine 5′-triphosphate (ATP) hydrolysis to substrate transport across biological membranes. Although many are promising drug targets, their mechanisms of modulation by small-molecule inhibitors remain largely unknown. Two first-generation inhibitors of the MsbA transporter, tetrahydrobenzothiophene 1 (TBT1) and G247, induce opposite effects on ATP hydrolysis. Using single-particle cryo–electron microscopy and functional assays, we show that TBT1 and G247 bind adjacent yet separate pockets in the MsbA transmembrane domains. Two TBT1 molecules asymmetrically occupy the substrate-binding site, which leads to a collapsed inward-facing conformation with decreased distance between the nucleotide-binding domains (NBDs). By contrast, two G247 molecules symmetrically increase NBD distance in a wide inward-open state of MsbA. The divergent mechanisms of action of these MsbA inhibitors provide important insights into ABC transporter pharmacology.
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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.