8ZRU

Structure of human ECHS1 in apo state

Summary for 8ZRU

• Entry DOI: 10.2210/pdb8zru/pdb
• EMDB information: 60405
• Descriptor: Enoyl-CoA hydratase, mitochondrial, MAGNESIUM ION (2 entities in total)
• Functional Keywords: echs1, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 6
• Total formula weight: 170302.21

Authors

Su, G.,Xu, Y.,Chen, B.,Ju, K.,Sun, X.,Jin, Y.,Liu, D.,Chen, H.,Zhang, S.,Luan, X. (deposition date: 2024-06-05, release date: 2025-04-30, Last modification date: 2025-07-02)

Primary citation

Su, G.,Xu, Y.,Chen, B.,Ju, K.,Jin, Y.,Chen, H.,Zhang, S.,Luan, X.
Structural and biochemical mechanism of short-chain enoyl-CoA hydratase (ECHS1) substrate recognition.
Commun Biol, 8:619-619, 2025

PubMed 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.

PubMed: 40240482
DOI: 10.1038/s42003-025-07924-0

Experimental method

ELECTRON MICROSCOPY (2.18 Å)