ArticleBiochemistry2022
Nanomolar, Noncovalent Antagonism of Hedgehog Cholesterolysis: Exception to the "Irreversibility Rule" for Protein Autoprocessing Inhibition.
Article in Biochemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 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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Who cites it
4 citing papers in PubMed, 6 citations in OpenAlex.
- In vitro reconstitution of vertebrate Sonic Hedgehog protein cholesterolysis.bioRxiv : the preprint server for biology · 2026Article
- There's more to enzyme antagonism than inhibition.Bioorganic & medicinal chemistry · 2023Review
- Paracatalytic induction: Subverting specificity in hedgehog protein autoprocessing with small molecules.Methods in enzymology · 2023Article
- Hedgehog Autoprocessing: From Structural Mechanisms to Drug Discovery.Frontiers in molecular biosciences · 2022Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Hedgehog (Hh) signaling ligands undergo carboxy terminal sterylation through specialized autoprocessing, called cholesterolysis. Sterylation is brought about intramolecularly in a single turnover by an adjacent enzymatic domain, called HhC, which is found in precursor Hh proteins only. Previous attempts to identify antagonists of the intramolecular activity of HhC have yielded inhibitors that bind HhC irreversibly through covalent mechanisms, as is common for protein autoprocessing inhibitors. Here, we report an exception to the "irreversibility rule" for autoprocessing inhibition. Using a fluorescence resonance energy transfer-based activity assay for HhC, we screened a focused library of sterol-like analogues for noncovalent inhibitors and identified and validated four structurally related molecules, which were then used for structure-activity relationship studies. The most effective derivative,
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Registered trials
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