ArticleMolecular cell2021
Structure, mechanism, and inhibition of Hedgehog acyltransferase.
Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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Who cites it
36 citing papers in PubMed, 54 citations in OpenAlex.
- Design principles of a membrane-spanning ubiquitin ligase.Molecular cell · 2026Article
- Trimbody with rigid AI-designed scaffolds enables atomic-resolution cryo-EM structure determination of small proteins.Nature communications · 2026Article
- Intracellular CaBMC molecular and cell biology · 2026Article
- Strategic advances for cryo-EM structural studies of small (<100 kDa) GPCRs.Communications biology · 2026Review
- Structural basis for Porcupine inhibition.Communications chemistry · 2025Article
- "Design principles of a membrane-spanning ubiquitin ligase".bioRxiv : the preprint server for biology · 2025Article
- Acyltransferases that Modify Cell Surface Polymers Across the Membrane.Biochemistry · 2025Review
- Martini 3 coarse-grained model of enzymes: Framework with validation by all-atom simulations and x-ray diffraction measurements.The Journal of chemical physics · 2025Article
- Probing the biological efficacy and mechanistic pathways of natural compounds in breast cancer therapy via the Hedgehog signaling pathway.Journal of pharmaceutical analysis · 2025Review
- Novel C-2 Aromatic Heterocycle-Substituted Triterpenoids Inhibit Hedgehog Signaling in GLI1 Overexpression Cancer Cells.ACS omega · 2025Article
- A Modular Customizable Ligand-Conjugate (LC) System Targeting GhrelinBiomolecules · 2025Article
- Peroxisome proliferator-activated receptors-mediated diabetic wound healing regulates endothelial cells' mitochondrial function via sonic hedgehog signaling.Burns & trauma · 2025Article
- Structural insights into the inhibition mechanism of fungal GWT1 by manogepix.Nature communications · 2024Article
- Structural insights into Frizzled3 through nanobody modulators.Nature communications · 2024Article
- Mapping structural and dynamic divergence across the MBOAT family.Structure (London, England : 1993) · 2024Article
- Structural insights into the transporting and catalyzing mechanism of DltB in LTA D-alanylation.Nature communications · 2024Article
- A Residual N-Terminal Peptide Enhances Signaling of Depalmitoylated Hedgehog to the Patched Receptor.Journal of developmental biology · 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
- Cryo-electron microscopy-based drug design.Frontiers in molecular biosciences · 2024Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
The Sonic Hedgehog (SHH) morphogen pathway is fundamental for embryonic development and stem cell maintenance and is implicated in various cancers. A key step in signaling is transfer of a palmitate group to the SHH N terminus, catalyzed by the multi-pass transmembrane enzyme Hedgehog acyltransferase (HHAT). We present the high-resolution cryo-EM structure of HHAT bound to substrate analog palmityl-coenzyme A and a SHH-mimetic megabody, revealing a heme group bound to HHAT that is essential for HHAT function. A structure of HHAT bound to potent small-molecule inhibitor IMP-1575 revealed conformational changes in the active site that occlude substrate binding. Our multidisciplinary analysis provides a detailed view of the mechanism by which HHAT adapts the membrane environment to transfer an acyl chain across the endoplasmic reticulum membrane. This structure of a membrane-bound O-acyltransferase (MBOAT) superfamily member provides a blueprint for other protein-substrate MBOATs and a template for future drug discovery.
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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.