Structural highlights
FunctionECHM_HUMAN Straight-chain enoyl-CoA thioesters from C4 up to at least C16 are processed, although with decreasing catalytic rate. Publication Abstract from PubMedDeficiency of short-chain enoyl-CoA hydratase (ECHS1), a crucial enzyme in fatty acid metabolism through the mitochondrial beta-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. Structural and biochemical mechanism of short-chain enoyl-CoA hydratase (ECHS1) substrate recognition.,Su G, Xu Y, Chen B, Ju K, Jin Y, Chen H, Zhang S, Luan X Commun Biol. 2025 Apr 16;8(1):619. doi: 10.1038/s42003-025-07924-0. PMID:40240482[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
This page was last modified 10:27, 30 April 2025.