ArticleNature structural & molecular biology2020
Molecular basis for acetyl-CoA production by ATP-citrate lyase.
Article in Nature structural & molecular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- The role of fatty acid metabolism in acute lung injury: a special focus on immunometabolism.Cellular and molecular life sciences : CMLS · 2024Pooled it
- Research progress on ATP-citrate lyase and its inhibitors: a metabolic-epigenetic perspective.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- De Novo Lipogenesis in Clear Cell Renal Cell Carcinoma: Mechanistic Insights and Therapeutic Implications.International journal of molecular sciences · 2026Review
- A cost-effective 200 kV cryo-EM core facility for high resolution single particle analysis.Methods in microscopy · 2026Article
- Pediococcus acidilactici PA-1 Alleviates Diet-Induced Obesity by Modulating Hepatic Amino Acid Metabolism and Gut Microbiota in Mice.Probiotics and antimicrobial proteins · 2026Article
- Role of ATP citrate lyase and its complementary partner on fatty acid synthesis in gastric cancer.Scientific reports · 2024Article
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- Hepatic malonyl-CoA synthesis restrains gluconeogenesis by suppressing fat oxidation, pyruvate carboxylation, and amino acid availability.Cell metabolism · 2024Article
- Integrated Transcriptomics and Metabolomics Reveal Changes in Cell Homeostasis and Energy Metabolism inInternational journal of molecular sciences · 2024Article
- Gut microbiome synthesizes important core metabolites to prevent cognitive decline and mitigate onset and progression of Alzheimer's disease.Journal of Alzheimer's disease reports · 2024Article
- Article
- Cryo-EM of a heterogeneous biochemical fraction elucidates multiple protein complexes from a multicellular thermophilic eukaryote.Journal of structural biology: X · 2023Article
- Metabolic regulation of proteome stability via N-terminal acetylation controls male germline stem cell differentiation and reproduction.Nature communications · 2023Article
- Early Solid Diet Supplementation Influences the Proteomics of Rumen Epithelium in Goat Kids.Biology · 2023Article
- Physiological and pathological roles of lipogenesis.Nature metabolism · 2023Review
- The mitochondrion ofProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Allosteric role of the citrate synthase homology domain of ATP citrate lyase.Nature communications · 2023Article
- Acetyl-CoA metabolism in cancer.Nature reviews. Cancer · 2023Review
- The structure of succinyl-CoA synthetase bound to the succinyl-phosphate intermediate clarifies the catalytic mechanism of ATP-citrate lyase.Acta crystallographica. Section F, Structural biology communications · 2022Article
Corrections and comments
- Commented on by
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- Erratum issued
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
ATP-citrate lyase (ACLY) synthesizes cytosolic acetyl coenzyme A (acetyl-CoA), a fundamental cellular building block. Accordingly, aberrant ACLY activity is observed in many diseases. Here we report cryo-EM structures of human ACLY, alone or bound to substrates or products. ACLY forms a homotetramer with a rigid citrate synthase homology (CSH) module, flanked by four flexible acetyl-CoA synthetase homology (ASH) domains; CoA is bound at the CSH-ASH interface in mutually exclusive productive or unproductive conformations. The structure of a catalytic mutant of ACLY in the presence of ATP, citrate and CoA substrates reveals a phospho-citryl-CoA intermediate in the ASH domain. ACLY with acetyl-CoA and oxaloacetate products shows the products bound in the ASH domain, with an additional oxaloacetate in the CSH domain, which could function in ACLY autoinhibition. These structures, which are supported by biochemical and biophysical data, challenge previous proposals of the ACLY catalytic mechanism and suggest additional therapeutic possibilities for ACLY-associated metabolic disorders.
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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.