ArticleCommunications biology2025
Structural and biochemical mechanism of short-chain enoyl-CoA hydratase (ECHS1) substrate recognition.
Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Integrated Multi-Omic Analyses Reveal Gender-Specific Molecular Mechanisms Regulating Growth and Muscle Development in Zhongshan Partridge Ducks.Biomolecules · 2026Article
- SUMOylation activates ECHS1 for adaptive catabolism in lung cancer.Cell death & disease · 2026Article
- Loss of Echs1 in neural stem and progenitor cells impairs neurogenesis via ER stress activation and lipid metabolic reprogramming.Nature communications · 2026Article
- Coming to light: the transcriptional regulatory roles of histone lysine crotonylation in health and disease.Cellular & molecular biology letters · 2026Review
- Gut Microbiota Dysbiosis Remodels the Lysine Acetylome of the Mouse Cecum in Early Life.Biology · 2025Article
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Authors and funding
8 authors.
Funding
Abstract
Deficiency of short-chain enoyl-CoA hydratase (ECHS1), a crucial enzyme in fatty acid metabolism through the mitochondrial β-oxidation pathway, has been strongly linked to various diseases, especially cardiomyopathy. However, the structural and biochemical mechanisms through which ECHS1 recognizes acyl-CoAs remain poorly understood. Herein, cryo-EM analysis reveals the apo structure of ECHS1 and structures of the ECHS1-crotonyl-CoA, ECHS1-acetoacetyl-CoA, ECHS1-hexanoyl-CoA, and ECHS1-octanoyl-CoA complexes at high resolutions. The mechanism through which ECHS1 recognizes its substrates varies with the fatty acid chain lengths of acyl-CoAs. Furthermore, crucial point mutations in ECHS1 have a great impact on substrate recognition, resulting in significant changes in binding affinity and enzyme activity, as do disease-related point mutations in ECHS1. The functional mechanism of ECHS1 is systematically elucidated from structural and biochemical perspectives. These findings provide a theoretical basis for subsequent work focused on determining the role of ECHS1 deficiency (ECHS1D) in the occurrence of diseases such as cardiomyopathy.
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Registered trials
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