ArticleProtein science : a publication of the Protein Society2020
Type I fatty acid synthase trapped in the octanoyl-bound state.
Article in Protein science : a publication of the Protein Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 47 citations in OpenAlex.
- Engineering metazoan fatty acid synthase to control chain length applied in yeast.Nature chemical biology · 2026Article
- Structural basis of product recognition by Mycobacterium tuberculosis fatty acid synthase.Protein science : a publication of the Protein Society · 2026Article
- The enzyme kinetics of branched-chain fatty acid synthesis of metazoan fatty acid synthase.Protein science : a publication of the Protein Society · 2025Article
- Article
- The structure of full-length AFPK supports the ACP linker in a role that regulates iterative polyketide and fatty acid assembly.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Kinetics of Carbon-Carbon Bond Formation in Metazoan Fatty Acid Synthase and Its Impact on Product Fidelity.Angewandte Chemie (International ed. in English) · 2025Article
- VCP enhances autophagy-related osteosarcoma progression by recruiting USP2 to inhibit ubiquitination and degradation of FASN.Cell death & disease · 2024Article
- The malonyl/acetyl-transferase from murine fatty acid synthase is a promiscuous engineering tool for editing polyketide scaffolds.Communications chemistry · 2024Article
- Modular polyketide synthase ketosynthases collaborate with upstream dehydratases to install double bonds.Chemical communications (Cambridge, England) · 2024Article
- Assessing and harnessing updated polyketide synthase modules through combinatorial engineering.Nature communications · 2024Article
- Fatty Acid Synthase as Interacting Anticancer Target of the Terpenoid Myrianthic Acid Disclosed by MS-Based Proteomics Approaches.International journal of molecular sciences · 2024Article
- Animal FAS-like polyketide synthases produce diverse polypropionates.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Kinetic data for modeling the dynamics of the enzymes involved in animal fatty acid synthesis.Bioscience reports · 2023Review
- Atomic model for core modifying region of human fatty acid synthase in complex with Denifanstat.Nature communications · 2023Article
- Acetyl-CoA-mediated autoacetylation of fatty acid synthase as a metabolic switch of de novo lipogenesis inProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Priming enzymes from the pikromycin synthase reveal how assembly-line ketosynthases catalyze carbon-carbon chemistry.Structure (London, England : 1993) · 2022Article
- Mechanism-based cross-linking probes capture the Escherichia coli ketosynthase FabB in conformationally distinct catalytic states.Acta crystallographica. Section D, Structural biology · 2022Article
- Benchmarking the Accuracy of AlphaFold 2 in Loop Structure Prediction.Biomolecules · 2022Article
- Enzymology of standalone elongating ketosynthases.Chemical science · 2022Review
- HowACS chemical biology · 2021Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
De novo fatty acid biosynthesis in humans is accomplished by a multidomain protein, the Type I fatty acid synthase (FAS). Although ubiquitously expressed in all tissues, fatty acid synthesis is not essential in normal healthy cells due to sufficient supply with fatty acids by the diet. However, FAS is overexpressed in cancer cells and correlates with tumor malignancy, which makes FAS an attractive selective therapeutic target in tumorigenesis. Herein, we present a crystal structure of the condensing part of murine FAS, highly homologous to human FAS, with octanoyl moieties covalently bound to the transferase (MAT-malonyl-/acetyltransferase) and the condensation (KS-β-ketoacyl synthase) domain. The MAT domain binds the octanoyl moiety in a novel (unique) conformation, which reflects the pronounced conformational dynamics of the substrate-binding site responsible for the MAT substrate promiscuity. In contrast, the KS binding pocket just subtly adapts to the octanoyl moiety upon substrate binding. Besides the rigid domain structure, we found a positive cooperative effect in the substrate binding of the KS domain by a comprehensive enzyme kinetic study. These structural and mechanistic findings contribute significantly to our understanding of the mode of action of FAS and may guide future rational inhibitor designs.
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