ArticleNature chemical biology2019
PH-domain-binding inhibitors of nucleotide exchange factor BRAG2 disrupt Arf GTPase signaling.
Article in Nature chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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.
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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.
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Who cites it
21 citing papers in PubMed, 47 citations in OpenAlex.
- Targeting a Pleckstrin Homology Domain with a Lysine-Reactive Covalent Binder.Journal of medicinal chemistry · 2026Article
- Controlled formation of versatile methylated compounds based on ring opening of 4-methyl-1-siloxy-1,4-epoxy-1,4-dihydrobenzene.RSC advances · 2026Article
- The cytokinesis regulator RacGAP1 is a Rac1-specific GAP on membranes.Protein science : a publication of the Protein Society · 2026Article
- Decoding Protein-Membrane Binding Interfaces from Surface-Fingerprint-Based Geometric Deep Learning and Molecular Dynamics Simulations.Journal of chemical information and modeling · 2026Article
- Structural and allosteric effects of the membrane-bound PI3Kα H1047R mutation and opportunities for drug discovery.Communications chemistry · 2025Article
- Discovery, Optimization, and Anticancer Activity of Lipid-Competitive Pleckstrin Homology Domain-Containing Family A Inhibitors.Journal of medicinal chemistry · 2025Article
- An active allosteric mechanism in ASAP1-mediated Arf1 GTP hydrolysis redefines PH domain function.Nature communications · 2025Article
- Article
- Emerging Approaches for Studying Lipid Dynamics, Metabolism, and Interactions in Cells.Annual review of biochemistry · 2025Review
- Evolution of a Strategy for the Total Synthesis of theChemistryEurope · 2025Article
- The PH domain in the ArfGAP ASAP1 drives catalytic activation through an unprecedented allosteric mechanism.bioRxiv : the preprint server for biology · 2024Article
- Small Molecule Modulator of the mTORC2 Pathway Discovered from a DEL Library Designed to Bind to Pleckstrin Homology Domains.ACS chemical biology · 2024Article
- A molten globule ensemble primes Arf1-GDP for the nucleotide switch.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Membrane trafficking alterations in breast cancer progression.Frontiers in cell and developmental biology · 2024Review
- Ca2+-induced release of IQSEC2/BRAG1 autoinhibition under physiological and pathological conditions.The Journal of cell biology · 2023Article
- Membranes prime the RapGEF EPAC1 to transduce cAMP signaling.Nature communications · 2023Article
- DREAMM: a web-based server for drugging protein-membrane interfaces as a novel workflow for targeted drug design.Bioinformatics (Oxford, England) · 2022Article
- Systematic simulation of the interactions of pleckstrin homology domains with membranes.Science advances · 2022Article
- Predicting protein-membrane interfaces of peripheral membrane proteins using ensemble machine learning.Briefings in bioinformatics · 2022Article
- In vitro fluorescence assay to measure GDP/GTP exchange of guanine nucleotide exchange factors of Rho family GTPases.Biology methods & protocols · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Peripheral membrane proteins orchestrate many physiological and pathological processes, making regulation of their activities by small molecules highly desirable. However, they are often refractory to classical competitive inhibition. Here, we demonstrate that potent and selective inhibition of peripheral membrane proteins can be achieved by small molecules that target protein-membrane interactions by a noncompetitive mechanism. We show that the small molecule Bragsin inhibits BRAG2-mediated Arf GTPase activation in vitro in a manner that requires a membrane. In cells, Bragsin affects the trans-Golgi network in a BRAG2- and Arf-dependent manner. The crystal structure of the BRAG2-Bragsin complex and structure-activity relationship analysis reveal that Bragsin binds at the interface between the PH domain of BRAG2 and the lipid bilayer to render BRAG2 unable to activate lipidated Arf. Finally, Bragsin affects tumorsphere formation in breast cancer cell lines. Bragsin thus pioneers a novel class of drugs that function by altering protein-membrane interactions without disruption.
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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.