ArticleThe Journal of pharmacology and experimental therapeutics2017
Lecithin:Cholesterol Acyltransferase Activation by Sulfhydryl-Reactive Small Molecules: Role of Cysteine-31.
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Article in The Journal of pharmacology and experimental therapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22citing papers in PubMed
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Who cites it
22 citing papers in PubMed, 43 citations in OpenAlex.
- Mutation of a single cysteine in CaMKIIδ protects the heart from ischemia-reperfusion Injury.bioRxiv : the preprint server for biology · 2026Article
- Cholesterol metabolism: molecular mechanisms, biological functions, diseases, and therapeutic targets.Molecular biomedicine · 2025Review
- Quo Vadis after AEGIS: New Opportunities for Therapies Targeted at Reverse Cholesterol Transport?Current atherosclerosis reports · 2025Review
- Gliflozins, sucrose and flavonoids are allosteric activators of lecithin-cholesterol acyltransferase.Scientific reports · 2024Article
- Targeting host-specific metabolic pathways-opportunities and challenges for anti-infective therapy.Frontiers in molecular biosciences · 2024Review
- N-Sulfenylation of β-Lactams: Radical Reaction ofThe Journal of organic chemistry · 2023Article
- Abnormal Lipoproteins Trigger Oxidative Stress-Mediated Apoptosis of Renal Cells in LCAT Deficiency.Antioxidants (Basel, Switzerland) · 2023Article
- HDL and chronic kidney disease.Atherosclerosis plus · 2023Article
- Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics.Signal transduction and targeted therapy · 2022Review
- The HDL mimetic CER-001 remodels plasma lipoproteins and reduces kidney lipid deposits in inherited lecithin:cholesterol acyltransferase deficiency.Journal of internal medicine · 2022Article
- Apolipoprotein A1-Related Proteins and Reverse Cholesterol Transport in Antiatherosclerosis Therapy: Recent Progress and Future Perspectives.Cardiovascular therapeutics · 2022Review
- Article
- High-Density Lipoproteins and the Kidney.Cells · 2021Review
- 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
- Controversial Role of Lecithin:Cholesterol Acyltransferase in the Development of Atherosclerosis: New Insights From an LCAT Activator.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Progression of chronic kidney disease in familial LCAT deficiency: a follow-up of the Italian cohort.Journal of lipid research · 2020Article
- Novel lecithin: cholesterol acyltransferase-based therapeutic approaches.Current opinion in lipidology · 2020Article
- LCAT protects against Lipoprotein-X formation in a murine model of drug-induced intrahepatic cholestasis.Pharmacology research & perspectives · 2020Article
- Article
- Interaction of lecithin:cholesterol acyltransferase with lipid surfaces and apolipoprotein A-I-derived peptides.Journal of lipid research · 2018Article
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Authors and funding
18 authors at 6 institutions in 2 countries.
Lita A FreemanLipid Metabolism Section, Cardiovascular and Pulmonary Branch (L.A.F., S.J.D., S.M.G., B.L.V., R.D.S., A.T.R.), Systems Biology Center (A.A., M.G.), and Laboratory of Biochemistry (R.L.L.), National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland; Department of Chemistry, American University, Washington, DC (M.K., R.K.); University of Milano, Milano, Italy (A.F.O., L.C.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (R.F.K.); Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan (K.A.M., J.J.G.T.); and National Institutes of Health National Center for Advancing Translational Sciences, Bethesda, Maryland (M.S., A.J.).
Stephen J DemoskyLipid Metabolism Section, Cardiovascular and Pulmonary Branch (L.A.F., S.J.D., S.M.G., B.L.V., R.D.S., A.T.R.), Systems Biology Center (A.A., M.G.), and Laboratory of Biochemistry (R.L.L.), National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland; Department of Chemistry, American University, Washington, DC (M.K., R.K.); University of Milano, Milano, Italy (A.F.O., L.C.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (R.F.K.); Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan (K.A.M., J.J.G.T.); and National Institutes of Health National Center for Advancing Translational Sciences, Bethesda, Maryland (M.S., A.J.).
Monika KonaklievaLipid Metabolism Section, Cardiovascular and Pulmonary Branch (L.A.F., S.J.D., S.M.G., B.L.V., R.D.S., A.T.R.), Systems Biology Center (A.A., M.G.), and Laboratory of Biochemistry (R.L.L.), National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland; Department of Chemistry, American University, Washington, DC (M.K., R.K.); University of Milano, Milano, Italy (A.F.O., L.C.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (R.F.K.); Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan (K.A.M., J.J.G.T.); and National Institutes of Health National Center for Advancing Translational Sciences, Bethesda, Maryland (M.S., A.J.).
Rostislav KuskovskyLipid Metabolism Section, Cardiovascular and Pulmonary Branch (L.A.F., S.J.D., S.M.G., B.L.V., R.D.S., A.T.R.), Systems Biology Center (A.A., M.G.), and Laboratory of Biochemistry (R.L.L.), National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland; Department of Chemistry, American University, Washington, DC (M.K., R.K.); University of Milano, Milano, Italy (A.F.O., L.C.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (R.F.K.); Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan (K.A.M., J.J.G.T.); and National Institutes of Health National Center for Advancing Translational Sciences, Bethesda, Maryland (M.S., A.J.).
Angel AponteLipid Metabolism Section, Cardiovascular and Pulmonary Branch (L.A.F., S.J.D., S.M.G., B.L.V., R.D.S., A.T.R.), Systems Biology Center (A.A., M.G.), and Laboratory of Biochemistry (R.L.L.), National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland; Department of Chemistry, American University, Washington, DC (M.K., R.K.); University of Milano, Milano, Italy (A.F.O., L.C.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (R.F.K.); Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan (K.A.M., J.J.G.T.); and National Institutes of Health National Center for Advancing Translational Sciences, Bethesda, Maryland (M.S., A.J.).
Alice F OssoliLipid Metabolism Section, Cardiovascular and Pulmonary Branch (L.A.F., S.J.D., S.M.G., B.L.V., R.D.S., A.T.R.), Systems Biology Center (A.A., M.G.), and Laboratory of Biochemistry (R.L.L.), National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland; Department of Chemistry, American University, Washington, DC (M.K., R.K.); University of Milano, Milano, Italy (A.F.O., L.C.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (R.F.K.); Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan (K.A.M., J.J.G.T.); and National Institutes of Health National Center for Advancing Translational Sciences, Bethesda, Maryland (M.S., A.J.).
Scott M GordonLipid Metabolism Section, Cardiovascular and Pulmonary Branch (L.A.F., S.J.D., S.M.G., B.L.V., R.D.S., A.T.R.), Systems Biology Center (A.A., M.G.), and Laboratory of Biochemistry (R.L.L.), National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland; Department of Chemistry, American University, Washington, DC (M.K., R.K.); University of Milano, Milano, Italy (A.F.O., L.C.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (R.F.K.); Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan (K.A.M., J.J.G.T.); and National Institutes of Health National Center for Advancing Translational Sciences, Bethesda, Maryland (M.S., A.J.).
Ross F KobyLipid Metabolism Section, Cardiovascular and Pulmonary Branch (L.A.F., S.J.D., S.M.G., B.L.V., R.D.S., A.T.R.), Systems Biology Center (A.A., M.G.), and Laboratory of Biochemistry (R.L.L.), National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland; Department of Chemistry, American University, Washington, DC (M.K., R.K.); University of Milano, Milano, Italy (A.F.O., L.C.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (R.F.K.); Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan (K.A.M., J.J.G.T.); and National Institutes of Health National Center for Advancing Translational Sciences, Bethesda, Maryland (M.S., A.J.).
Kelly A MantheiLipid Metabolism Section, Cardiovascular and Pulmonary Branch (L.A.F., S.J.D., S.M.G., B.L.V., R.D.S., A.T.R.), Systems Biology Center (A.A., M.G.), and Laboratory of Biochemistry (R.L.L.), National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland; Department of Chemistry, American University, Washington, DC (M.K., R.K.); University of Milano, Milano, Italy (A.F.O., L.C.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (R.F.K.); Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan (K.A.M., J.J.G.T.); and National Institutes of Health National Center for Advancing Translational Sciences, Bethesda, Maryland (M.S., A.J.).
Min ShenLipid Metabolism Section, Cardiovascular and Pulmonary Branch (L.A.F., S.J.D., S.M.G., B.L.V., R.D.S., A.T.R.), Systems Biology Center (A.A., M.G.), and Laboratory of Biochemistry (R.L.L.), National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland; Department of Chemistry, American University, Washington, DC (M.K., R.K.); University of Milano, Milano, Italy (A.F.O., L.C.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (R.F.K.); Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan (K.A.M., J.J.G.T.); and National Institutes of Health National Center for Advancing Translational Sciences, Bethesda, Maryland (M.S., A.J.).
Boris L VaismanLipid Metabolism Section, Cardiovascular and Pulmonary Branch (L.A.F., S.J.D., S.M.G., B.L.V., R.D.S., A.T.R.), Systems Biology Center (A.A., M.G.), and Laboratory of Biochemistry (R.L.L.), National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland; Department of Chemistry, American University, Washington, DC (M.K., R.K.); University of Milano, Milano, Italy (A.F.O., L.C.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (R.F.K.); Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan (K.A.M., J.J.G.T.); and National Institutes of Health National Center for Advancing Translational Sciences, Bethesda, Maryland (M.S., A.J.).
Robert D ShamburekLipid Metabolism Section, Cardiovascular and Pulmonary Branch (L.A.F., S.J.D., S.M.G., B.L.V., R.D.S., A.T.R.), Systems Biology Center (A.A., M.G.), and Laboratory of Biochemistry (R.L.L.), National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland; Department of Chemistry, American University, Washington, DC (M.K., R.K.); University of Milano, Milano, Italy (A.F.O., L.C.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (R.F.K.); Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan (K.A.M., J.J.G.T.); and National Institutes of Health National Center for Advancing Translational Sciences, Bethesda, Maryland (M.S., A.J.).
Ajit JadhavLipid Metabolism Section, Cardiovascular and Pulmonary Branch (L.A.F., S.J.D., S.M.G., B.L.V., R.D.S., A.T.R.), Systems Biology Center (A.A., M.G.), and Laboratory of Biochemistry (R.L.L.), National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland; Department of Chemistry, American University, Washington, DC (M.K., R.K.); University of Milano, Milano, Italy (A.F.O., L.C.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (R.F.K.); Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan (K.A.M., J.J.G.T.); and National Institutes of Health National Center for Advancing Translational Sciences, Bethesda, Maryland (M.S., A.J.).
Laura CalabresiLipid Metabolism Section, Cardiovascular and Pulmonary Branch (L.A.F., S.J.D., S.M.G., B.L.V., R.D.S., A.T.R.), Systems Biology Center (A.A., M.G.), and Laboratory of Biochemistry (R.L.L.), National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland; Department of Chemistry, American University, Washington, DC (M.K., R.K.); University of Milano, Milano, Italy (A.F.O., L.C.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (R.F.K.); Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan (K.A.M., J.J.G.T.); and National Institutes of Health National Center for Advancing Translational Sciences, Bethesda, Maryland (M.S., A.J.).
Marjan GucekLipid Metabolism Section, Cardiovascular and Pulmonary Branch (L.A.F., S.J.D., S.M.G., B.L.V., R.D.S., A.T.R.), Systems Biology Center (A.A., M.G.), and Laboratory of Biochemistry (R.L.L.), National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland; Department of Chemistry, American University, Washington, DC (M.K., R.K.); University of Milano, Milano, Italy (A.F.O., L.C.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (R.F.K.); Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan (K.A.M., J.J.G.T.); and National Institutes of Health National Center for Advancing Translational Sciences, Bethesda, Maryland (M.S., A.J.).
John J G TesmerLipid Metabolism Section, Cardiovascular and Pulmonary Branch (L.A.F., S.J.D., S.M.G., B.L.V., R.D.S., A.T.R.), Systems Biology Center (A.A., M.G.), and Laboratory of Biochemistry (R.L.L.), National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland; Department of Chemistry, American University, Washington, DC (M.K., R.K.); University of Milano, Milano, Italy (A.F.O., L.C.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (R.F.K.); Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan (K.A.M., J.J.G.T.); and National Institutes of Health National Center for Advancing Translational Sciences, Bethesda, Maryland (M.S., A.J.).
Rodney L LevineLipid Metabolism Section, Cardiovascular and Pulmonary Branch (L.A.F., S.J.D., S.M.G., B.L.V., R.D.S., A.T.R.), Systems Biology Center (A.A., M.G.), and Laboratory of Biochemistry (R.L.L.), National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland; Department of Chemistry, American University, Washington, DC (M.K., R.K.); University of Milano, Milano, Italy (A.F.O., L.C.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (R.F.K.); Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan (K.A.M., J.J.G.T.); and National Institutes of Health National Center for Advancing Translational Sciences, Bethesda, Maryland (M.S., A.J.).
Alan T RemaleyLipid Metabolism Section, Cardiovascular and Pulmonary Branch (L.A.F., S.J.D., S.M.G., B.L.V., R.D.S., A.T.R.), Systems Biology Center (A.A., M.G.), and Laboratory of Biochemistry (R.L.L.), National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland; Department of Chemistry, American University, Washington, DC (M.K., R.K.); University of Milano, Milano, Italy (A.F.O., L.C.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (R.F.K.); Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan (K.A.M., J.J.G.T.); and National Institutes of Health National Center for Advancing Translational Sciences, Bethesda, Maryland (M.S., A.J.) aremaley1@mail.nih.gov.
American University · USUniversity of Milan · ITVanderbilt University · USNational Center for Advancing Translational Sciences · USUniversity of Michigan–Ann Arbor · USNational Institutes of Health · US
Funding
Oxidative Modification Of ProteinsZIAHL000225 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI LEVINE, RODNEY L. · 2009 to 2025
$35.2MProteomics CoreZICHL005903 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI GUCEK, MARJAN · 2009 to 2022
$23.3MDevelopment of recombinant Lecithin Cholesterol Acyltransferase as a therapeuticZIAHL006092 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI REMALEY, ALAN THOMAS · 2010 to 2021
$13.0MStructure, function, and inhibition of G protein-coupled receptor kinasesR01HL071818 · NHLBI · UNIVERSITY OF TEXAS AUSTIN · PI TESMER, JOHN · 2004 to 2023
$7.1MStructure and Function of the LPLA2/LCAT Acyltransferase FamilyR01HL122416 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TESMER, JOHN · 2015 to 2018
$1.9MStructural and functional studies of lecithin:cholesterol acyltransferaseF32HL131288 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MANTHEI, KELLY A · 2016 to 2018
$179kNHLBI NIH HHS F32 HL131288NHLBI NIH HHS R01 HL071818NHLBI NIH HHS R01 HL122416
Abstract
Lecithin:cholesterol acyltransferase (LCAT) catalyzes plasma cholesteryl ester formation and is defective in familial lecithin:cholesterol acyltransferase deficiency (FLD), an autosomal recessive disorder characterized by low high-density lipoprotein, anemia, and renal disease. This study aimed to investigate the mechanism by which compound A [3-(5-(ethylthio)-1,3,4-thiadiazol-2-ylthio)pyrazine-2-carbonitrile], a small heterocyclic amine, activates LCAT. The effect of compound A on LCAT was tested in human plasma and with recombinant LCAT. Mass spectrometry and nuclear magnetic resonance were used to determine compound A adduct formation with LCAT. Molecular modeling was performed to gain insight into the effects of compound A on LCAT structure and activity. Compound A increased LCAT activity in a subset (three of nine) of LCAT mutations to levels comparable to FLD heterozygotes. The site-directed mutation LCAT-Cys31Gly prevented activation by compound A. Substitution of Cys31 with charged residues (Glu, Arg, and Lys) decreased LCAT activity, whereas bulky hydrophobic groups (Trp, Leu, Phe, and Met) increased activity up to 3-fold (
Indexed as
CysteineDose-Response Relationship, DrugEnzyme ActivationEnzyme ActivatorsHEK293 CellsHumansLecithin Cholesterol Acyltransferase DeficiencyModels, MolecularPhosphatidylcholine-Sterol O-AcyltransferaseSulfhydryl CompoundsCysteineEnzyme ActivatorsPhosphatidylcholine-Sterol O-AcyltransferaseSulfhydryl Compounds
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