ArticleStructure (London, England : 1993)2021
Molecular structures of human ACAT2 disclose mechanism for selective inhibition.
Article in Structure (London, England : 1993), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Essential Biology of Lipid Droplets.Annual review of biochemistry · 2025Review
- Acyltransferases that Modify Cell Surface Polymers Across the Membrane.Biochemistry · 2025Review
- ACAT2 negatively modulated by FOXA2 suppresses ferroptosis to expedite the aggressive phenotypes of endometrial cancer cells.Histology and histopathology · 2025Article
- Albumin-Based Nanoparticles with Factorial Design as a Promising Approach for Remodeled Repaglinide: Evidence from In Silico, In Vitro, and In Vivo Evaluations.Pharmaceutics · 2025Article
- Mechanism and therapeutic potential of liver injury induced by cholesterol-associated proteins.Frontiers in pharmacology · 2025Review
- Celludinone C, a new dihydroisobenzofuran isolated from Talaromyces cellulolyticus BF-0307.The Journal of antibiotics · 2025Article
- Discovery of selective ACAT2 antagonist via a combination strategy based on deep docking, pharmacophore modelling, and molecular dynamics simulation.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- Mapping structural and dynamic divergence across the MBOAT family.Structure (London, England : 1993) · 2024Article
- Combined Computational-Biochemical Approach Offers an Accelerated Path to Membrane Protein Solubilization.Journal of chemical information and modeling · 2023Article
- Cryo-EM structures of Myomaker reveal a molecular basis for myoblast fusion.Nature structural & molecular biology · 2023Article
- Lipid droplet biogenesis and functions in health and disease.Nature reviews. Endocrinology · 2023Review
- Glycerolipid Synthesis and Lipid Droplet Formation in the Endoplasmic Reticulum.Cold Spring Harbor perspectives in biology · 2023Review
- A rising tide lifts all MBOATs: recent progress in structural and functional understanding of membrane boundFrontiers in physiology · 2023Review
- Article
- Structural enzymology of cholesterol biosynthesis and storage.Current opinion in structural biology · 2022Review
- Cholesterol efflux mechanism revealed by structural analysis of human ABCA1 conformational states.Nature cardiovascular research · 2022Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Endoplasmic reticulum-localized acyl-CoA:cholesterol acyltransferases (ACAT), including ACAT1 and ACAT2, convert cholesterol to cholesteryl esters that become incorporated into lipoproteins or stored in cytosolic lipid droplets. Selective inhibition of ACAT2 has been shown to considerably attenuate hypercholesterolemia and atherosclerosis in mice. Here, we report cryogenic electron microscopy structures of human ACAT2 bound to its specific inhibitor pyripyropene A or the general ACAT inhibitor nevanimibe. Structural analysis reveals that ACAT2 has a topology in membranes similar to that of ACAT1. A catalytic core with an entry site occupied by a cholesterol molecule and another site for allosteric activation of ACAT2 is observed in these structures. Enzymatic assays show that mutations within sites of cholesterol entry or allosteric activation attenuate ACAT2 activity in vitro. Together, these results reveal mechanisms for ACAT2-mediated esterification of cholesterol, providing a blueprint to design new ACAT2 inhibitors for use in the prevention of cardiovascular disease.
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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.