8ZRV

Structure of human ECHS1 in complex with Hexanoyl-CoA

8ZRV の概要

• エントリーDOI: 10.2210/pdb8zrv/pdb
• EMDBエントリー: 60406
• 分子名称: Enoyl-CoA hydratase, mitochondrial, HEXANOYL-COENZYME A, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: echs1, hexanoyl-coa, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 175496.27

構造登録者

Su, G.,Xu, Y.,Chen, B.,Ju, K.,Sun, X.,Jin, Y.,Liu, D.,Chen, H.,Zhang, S.,Luan, X. (登録日: 2024-06-05, 公開日: 2025-04-30)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (2.55 Å)