ArticleThe Journal of biological chemistry2014
Structural basis for regulation of the human acetyl-CoA thioesterase 12 and interactions with the steroidogenic acute regulatory protein-related lipid transfer (START) domain.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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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Who cites it
15 citing papers in PubMed, 29 citations in OpenAlex.
- Fatty acid metabolism and the oxidative stress response support bacterial predation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Structure, function, and lipid sensing activity in the thioesterase superfamily.Biochemical Society transactions · 2024Review
- Article
- Engineering of thioesterase YciA from Haemophilus influenzae for production of carboxylic acids.Applied microbiology and biotechnology · 2023Article
- Identification of a key geneFood chemistry. Molecular sciences · 2022Article
- Thioesterase enzyme families: Functions, structures, and mechanisms.Protein science : a publication of the Protein Society · 2022Article
- Loss of Acot12 contributes to NAFLD independent of lipolysis of adipose tissue.Experimental & molecular medicine · 2021Article
- Allosteric regulation of thioesterase superfamily member 1 by lipid sensor domain binding fatty acids and lysophosphatidylcholine.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Variation at ACOT12 and CT62 locus represents susceptibility to psoriasis in Han population.Molecular genetics & genomic medicine · 2020Article
- Acetate Revisited: A Key Biomolecule at the Nexus of Metabolism, Epigenetics and Oncogenesis-Part 1: Acetyl-CoA, Acetogenesis and Acyl-CoA Short-Chain Synthetases.Frontiers in physiology · 2020Review
- Farnesol induces fatty acid oxidation and decreases triglyceride accumulation in steatotic HepaRG cells.Toxicology and applied pharmacology · 2019Article
- Structural insights into GDP-mediated regulation of a bacterial acyl-CoA thioesterase.The Journal of biological chemistry · 2017Article
- Deactivating Fatty Acids: Acyl-CoA Thioesterase-Mediated Control of Lipid Metabolism.Trends in endocrinology and metabolism: TEM · 2017Review
- Structural and Functional Characterization of the PaaI Thioesterase from Streptococcus pneumoniae Reveals a Dual Specificity for Phenylacetyl-CoA and Medium-chain Fatty Acyl-CoAs and a Novel CoA-induced Fit Mechanism.The Journal of biological chemistry · 2016Article
- Structural and functional characterization of TesB from Yersinia pestis reveals a unique octameric arrangement of hotdog domains.Acta crystallographica. Section D, Biological crystallography · 2015Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acetyl-CoA plays a fundamental role in cell signaling and metabolic pathways, with its cellular levels tightly controlled through reciprocal regulation of enzymes that mediate its synthesis and catabolism. ACOT12, the primary acetyl-CoA thioesterase in the liver of human, mouse, and rat, is responsible for cleavage of the thioester bond within acetyl-CoA, producing acetate and coenzyme A for a range of cellular processes. The enzyme is regulated by ADP and ATP, which is believed to be mediated through the ligand-induced oligomerization of the thioesterase domains, whereby ATP induces active dimers and tetramers, whereas apo- and ADP-bound ACOT12 are monomeric and inactive. Here, using a range of structural and biophysical techniques, it is demonstrated that ACOT12 is a trimer rather than a tetramer and that neither ADP nor ATP exert their regulatory effects by altering the oligomeric status of the enzyme. Rather, the binding site and mechanism of ADP regulation have been determined to occur through two novel regulatory regions, one involving a large loop that links the thioesterase domains (Phe(154)-Thr(178)), defined here as RegLoop1, and a second region involving the C terminus of thioesterase domain 2 (Gln(304)-Gly(326)), designated RegLoop2. Mutagenesis confirmed that Arg(312) and Arg(313) are crucial for this mode of regulation, and novel interactions with the START domain are presented together with insights into domain swapping within eukaryotic thioesterases for substrate recognition. In summary, these experiments provide the first structural insights into the regulation of this enzyme family, revealing an alternate hypothesis likely to be conserved throughout evolution.
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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.