ArticleProceedings of the National Academy of Sciences of the United States of America2010
Structural basis for the specific inhibition of heterotrimeric Gq protein by a small molecule.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
141 citing papers in PubMed, 252 citations in OpenAlex.
- Structural basis of stepwise G protein activation by the viral chemokine receptor US28.bioRxiv : the preprint server for biology · 2026Article
- Small-molecule inhibitor of Gαo for GNAO1 encephalopathy.Bioscience reports · 2026Article
- TRH can stimulate the release of two POMC-derived pituitary hormones, ACTH and MSH, in medaka.Endocrinology · 2026Article
- Conformational biosensors delineate endosomal G protein regulation by GPCRs.Nature communications · 2026Article
- Sulfolipid-1 fromJournal of neurophysiology · 2026Article
- Intracellular calcium release activates carotid body afferents by fentanyl.Function (Oxford, England) · 2026Article
- Deciphering a mechanistic basis for the pathological effect of the GNAO1 E246K variant in neurodevelopmental disorder.BBA advances · 2026Article
- The G Protein Inhibitor YM-254890 is an Allosteric Glue.Journal of molecular biology · 2025Article
- Contractions of ex-vivo mouse bladder driven by activation of channelrhodopsin-2 expressed in urothelial cells.Scientific reports · 2025Article
- The thiazolidinedione drug troglitazone inhibits Gq signaling through direct binding to the Gq alpha subunit through inhibition of GDP release.Molecular pharmacology · 2025Article
- Inside-Out IPFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- APurinergic signalling · 2025Article
- Cyclic peptide inhibitors function as molecular glues to stabilize Gq/11 heterotrimers.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The guanine nucleotide exchange factor Ric-8A regulates the sensitivity of constitutively active Gαq to the inhibitor YM-254890.The Journal of biological chemistry · 2025Article
- The Gq/11 family of Gα subunits is necessary and sufficient for lower jaw development.Development (Cambridge, England) · 2025Article
- A2B adenosine receptor-triggered intracellular calcium mobilization: Cell type-dependent involvement of Gi, Gq, Gs proteins and protein kinase C.Research square · 2024Article
- The G protein inhibitor YM-254890 is an allosteric glue.bioRxiv : the preprint server for biology · 2024Article
- Functional bias of contractile control in mouse resistance arteries.Scientific reports · 2024Article
- Going Rogue: Mechanisms, Regulation, and Roles of Mutationally Activated GMolecular pharmacology · 2024Review
- Stabilization of interdomain closure by a G protein inhibitor.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
81 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heterotrimeric GTP-binding proteins (G proteins) transmit extracellular stimuli perceived by G protein-coupled receptors (GPCRs) to intracellular signaling cascades. Hundreds of GPCRs exist in humans and are the targets of a large percentage of the pharmaceutical drugs used today. Because G proteins are regulated by GPCRs, small molecules that directly modulate G proteins have the potential to become therapeutic agents. However, strategies to develop modulators have been hampered by a lack of structural knowledge of targeting sites for specific modulator binding. Here we present the mechanism of action of the cyclic depsipeptide YM-254890, which is a recently discovered Gq-selective inhibitor. YM-254890 specifically inhibits the GDP/GTP exchange reaction of alpha subunit of Gq protein (Galphaq) by inhibiting the GDP release from Galphaq. X-ray crystal structure analysis of the Galphaqbetagamma-YM-254890 complex shows that YM-254890 binds the hydrophobic cleft between two interdomain linkers connecting the GTPase and helical domains of the Galphaq. The binding stabilizes an inactive GDP-bound form through direct interactions with switch I and impairs the linker flexibility. Our studies provide a novel targeting site for the development of small molecules that selectively inhibit each Galpha subunit and an insight into the molecular mechanism of G protein activation.
Indexed as
Identifiers
What OpenQuestion holds
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.