ArticleBiochimica et biophysica acta2011
Direct-reversible binding of small molecules to G protein βγ subunits.
Article in Biochimica et biophysica acta, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- MDA-9/Syntenin small molecule inhibitor IVMT-Rx-4 blocks prostate cancer bone metastasis.Pharmacological research · 2026Article
- GPR88 promotes neurite outgrowth of sensory neurons via activation of GFrontiers in pharmacology · 2025Article
- A neurodevelopmental disorder mutation locks G proteins in the transitory pre-activated state.Nature communications · 2024Article
- Biasing GMolecular pharmacology · 2024Article
- Article
- Aβ Assemblies Promote Amyloidogenic Processing of APP and Intracellular Accumulation of Aβ42 Through Go/Gβγ Signaling.Frontiers in cell and developmental biology · 2022Article
- A universal allosteric mechanism for G protein activation.Molecular cell · 2021Article
- Targeting G protein-coupled receptor signalling by blocking G proteins.Nature reviews. Drug discovery · 2018Review
- Intrinsic plasticity induced by group II metabotropic glutamate receptors via enhancement of high-threshold KV currents in sound localizing neurons.Neuroscience · 2016Article
- Inhibition of G-Protein βγ Signaling Decreases Levels of Messenger RNAs Encoding Proinflammatory Cytokines in T Cell Receptor-Stimulated CD4(+) T Helper Cells.Journal of molecular signaling · 2015Article
- Daple is a novel non-receptor GEF required for trimeric G protein activation in Wnt signaling.eLife · 2015Article
- Targeting G protein coupled receptor-related pathways as emerging molecular therapies.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2015Review
- Inhibition of G-protein βγ signaling enhances T cell receptor-stimulated interleukin 2 transcription in CD4+ T helper cells.PloS one · 2015Article
- A chemical biology approach demonstrates G protein βγ subunits are sufficient to mediate directional neutrophil chemotaxis.The Journal of biological chemistry · 2014Article
- Pharmacological profile of phosphatidylinositol 3-kinases and related phosphatidylinositols mediating endothelin(A) receptor-operated native TRPC channels in rabbit coronary artery myocytes.British journal of pharmacology · 2012Article
- Understanding molecular recognition by G protein βγ subunits on the path to pharmacological targeting.Molecular pharmacology · 2011Review
- Mechanisms for enhancement of μ-opioid receptor-mediated antinociception in the central nervous system through gallein-dependent modulation of downstream G protein βγ subunit signaling.Molecular pharmacologyArticle
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Heterotrimeric guanine nucleotide-binding proteins (G proteins) composed of three subunits α, β, γ mediate activation of multiple intracellular signaling cascades initiated by G protein-coupled receptors (GPCRs). Previously our laboratory identified small molecules that bind to Gβγ and interfere with or enhance binding of select effectors with Gβγ. To understand the molecular mechanisms of selectivity and assess binding of compounds to Gβγ, we used biophysical and biochemical approaches to directly monitor small molecule binding to Gβγ. Surface plasmon resonance (SPR) analysis indicated that multiple compounds bound directly to Gβγ with affinities in the high nanomolar to low micromolar range but with surprisingly slow on and off rate kinetics. While the k(off) was slow for most of the compounds in physiological buffers, they could be removed from Gβγ with mild chaotropic salts or mildly dissociating collision energy in a mass-spectrometer indicating that compound-Gβγ interactions were non-covalent. Finally, at concentrations used to observe maximal biological effects the stoichiometry of binding was 1:1. The results from this study show that small molecule modulation of Gβγ-effector interactions is by specific direct non-covalent and reversible binding of small molecules to Gβγ. This is highly relevant to development of Gβγ targeting as a therapeutic approach since reversible, direct binding is a prerequisite for drug development and important for specificity.
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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.