ArticleScience (New York, N.Y.)2021
Substrate and product complexes reveal mechanisms of Hedgehog acylation by HHAT.
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 38 papers.
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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
38 citing papers in PubMed, 58 citations in OpenAlex.
- Cryo-EM structure of TMEM164 reveals distinct phospholipid remodeling mechanisms with anti-ferroptotic potential.Nature communications · 2025Article
- Structural basis for Porcupine inhibition.Communications chemistry · 2025Article
- Protein palmitoylation: A potential therapeutic target in cardiovascular diseases.Acta pharmaceutica Sinica. B · 2025Review
- Cancer-Associated Fibroblasts: Heterogeneity, Cancer Pathogenesis, and Therapeutic Targets.MedComm · 2025Review
- Acyltransferases that Modify Cell Surface Polymers Across the Membrane.Biochemistry · 2025Review
- A Modular Customizable Ligand-Conjugate (LC) System Targeting GhrelinBiomolecules · 2025Article
- Structural insights into the inhibition mechanism of fungal GWT1 by manogepix.Nature communications · 2024Article
- Article
- Structure and mechanism of lysosome transmembrane acetylation by HGSNAT.Nature structural & molecular biology · 2024Article
- 1-L Transcription in Prion Diseases.International journal of molecular sciences · 2024Article
- Mapping structural and dynamic divergence across the MBOAT family.Structure (London, England : 1993) · 2024Article
- Is the Hedgehog Pathway Involved in the Pathophysiology of Schizophrenia? A Systematic Review of Current Evidence of Neural Molecular Correlates and Perspectives on Drug Development.Current issues in molecular biology · 2024Review
- Structural insights into the transporting and catalyzing mechanism of DltB in LTA D-alanylation.Nature communications · 2024Article
- Protein lipidation in cancer: mechanisms, dysregulation and emerging drug targets.Nature reviews. Cancer · 2024Review
- Design, Synthesis, and Evaluation of Inhibitors of Hedgehog Acyltransferase.Journal of medicinal chemistry · 2024Article
- Transcriptomics-based anti-tuberculous mechanism of traditional Chinese polyherbal preparation NiuBeiXiaoHe intermediates.Frontiers in pharmacology · 2024Article
- Structure and mechanism of a eukaryotic ceramide synthase complex.The EMBO journal · 2023Article
- Combined Computational-Biochemical Approach Offers an Accelerated Path to Membrane Protein Solubilization.Journal of chemical information and modeling · 2023Article
- Cellular and molecular mechanisms of Hedgehog signalling.Nature reviews. Molecular cell biology · 2023Review
- Cellular Uptake of a Fluorescent Ligand Reveals GhrelinACS chemical biology · 2023Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Hedgehog proteins govern crucial developmental steps in animals and drive certain human cancers. Before they can function as signaling molecules, Hedgehog precursor proteins must undergo amino-terminal palmitoylation by Hedgehog acyltransferase (HHAT). We present cryo-electron microscopy structures of human HHAT in complex with its palmitoyl-coenzyme A substrate and of a product complex with a palmitoylated Hedgehog peptide at resolutions of 2.7 and 3.2 angstroms, respectively. The structures reveal how HHAT overcomes the challenges of bringing together substrates that have different physiochemical properties from opposite sides of the endoplasmic reticulum membrane within a membrane-embedded active site for catalysis. These principles are relevant to related enzymes that catalyze the acylation of Wnt and of the appetite-stimulating hormone ghrelin. The structural and mechanistic insights may advance the development of inhibitors for cancer.
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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.