ArticleeLife2018
Molecular basis for activation of lecithin:cholesterol acyltransferase by a compound that increases HDL cholesterol.
Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed, 47 citations in OpenAlex.
- Postpartum lipid dysregulation in African American women who experienced cardiometabolic complications of pregnancy.iScience · 2025Article
- Lecithin:cholesterol acyltransferase binds a discontinuous binding site on adjacent apolipoprotein A-I belts in HDL.Journal of lipid research · 2025Article
- Gliflozins, sucrose and flavonoids are allosteric activators of lecithin-cholesterol acyltransferase.Scientific reports · 2024Article
- Rescue of Familial Lecithin:Cholesterol Acyltranferase Deficiency Mutations with an Allosteric Activator.Molecular pharmacology · 2024Article
- Systematic evaluation of lecithin:cholesterol acyltransferase binding sites in apolipoproteins via peptide based nanodiscs: regulatory role of charged residues at positions 4 and 7.PLoS computational biology · 2024Article
- Targeting host-specific metabolic pathways-opportunities and challenges for anti-infective therapy.Frontiers in molecular biosciences · 2024Review
- Familial LCAT Deficiency and Low HDL-C Levels: In silico Characterization of Two Rare LCAT Missense Mutations.The application of clinical genetics · 2024Article
- Abnormal Lipoproteins Trigger Oxidative Stress-Mediated Apoptosis of Renal Cells in LCAT Deficiency.Antioxidants (Basel, Switzerland) · 2023Article
- Effects of superoxide anion attack on the lipoprotein HDL.Molecular and cellular biochemistry · 2023Article
- Mechanistic Insights into the Activation of Lecithin-Cholesterol Acyltransferase in Therapeutic Nanodiscs Composed of Apolipoprotein A-I Mimetic Peptides and Phospholipids.Molecular pharmaceutics · 2022Article
- Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics.Signal transduction and targeted therapy · 2022Review
- Caecal microbiota could effectively increase chicken growth performance by regulating fat metabolism.Microbial biotechnology · 2022Article
- Influence of lecithin cholesterol acyltransferase alteration during different pathophysiologic conditions: A 45 years bibliometrics analysis.Frontiers in pharmacology · 2022Article
- Positive allosteric modulators of lecithin: Cholesterol acyltransferase adjust the orientation of the membrane-binding domain and alter its spatial free energy profile.PLoS computational biology · 2021Article
- rHDL modeling and the anchoring mechanism of LCAT activation.Journal of lipid research · 2021Article
- Controversial Role of Lecithin:Cholesterol Acyltransferase in the Development of Atherosclerosis: New Insights From an LCAT Activator.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- A Plasma Protein Network Regulates PM20D1 and N-Acyl Amino Acid Bioactivity.Cell chemical biology · 2020Article
- Lecithin:cholesterol acyltransferase: symposium on 50 years of biomedical research from its discovery to latest findings.Journal of lipid research · 2020Article
- Novel lecithin: cholesterol acyltransferase-based therapeutic approaches.Current opinion in lipidology · 2020Article
- Bioinformatics-based screening of key genes for transformation of liver cirrhosis to hepatocellular carcinoma.Journal of translational medicine · 2020Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Lecithin:cholesterol acyltransferase (LCAT) and LCAT-activating compounds are being investigated as treatments for coronary heart disease (CHD) and familial LCAT deficiency (FLD). Herein we report the crystal structure of human LCAT in complex with a potent piperidinylpyrazolopyridine activator and an acyl intermediate-like inhibitor, revealing LCAT in an active conformation. Unlike other LCAT activators, the piperidinylpyrazolopyridine activator binds exclusively to the membrane-binding domain (MBD). Functional studies indicate that the compound does not modulate the affinity of LCAT for HDL, but instead stabilizes residues in the MBD and facilitates channeling of substrates into the active site. By demonstrating that these activators increase the activity of an FLD variant, we show that compounds targeting the MBD have therapeutic potential. Our data better define the substrate binding site of LCAT and pave the way for rational design of LCAT agonists and improved biotherapeutics for augmenting or restoring reverse cholesterol transport in CHD and FLD patients.
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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.