8ZRY

Structure of human ECHS1 in complex with Crotonoyl-CoA

これはPDB形式変換不可エントリーです。

8ZRY の概要

• エントリーDOI: 10.2210/pdb8zry/pdb
• EMDBエントリー: 60409
• 分子名称: Enoyl-CoA hydratase, mitochondrial, S-[2-[3-[[(2R)-4-[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-oxidanyl-3-phosphonooxy-oxolan-2-yl]methoxy-oxidanyl-phosphoryl]oxy-oxidanyl-phosphoryl]oxy-3,3-dimethyl-2-oxidanyl-butanoyl]amino]propanoylamino]ethyl] (E)-but-2-enethioate, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: echs1, crotonoyl-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: 175315.86

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 (2.23 Å)