Structural and biochemical mechanism of short-chain enoyl-CoA hydratase (ECHS1) substrate recognition
文献类型：期刊论文
| 作者 | Su, Gengchen6,7; Xu, Youwei5; Chen, Binxian6; Ju, Kaide6; Jin, Ye7; Chen, Houzao4; Zhang, Shuyang1,3,6,7; Luan, Xiaodong2,7 |
| 刊名 | COMMUNICATIONS BIOLOGY
 |
| 出版日期 | 2025-04-16 |
| 卷号 | 8期号:1页码:12 |
| DOI | 10.1038/s42003-025-07924-0 |
| 通讯作者 | Chen, Houzao(chenhouzao@ibms.cams.cn) ; Zhang, Shuyang(shuyangzhang103@nrdrs.org) ; Luan, Xiaodong(luanxiaodong@pumch.cn) |
| 英文摘要 | Deficiency 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. |
| WOS关键词 | CRYSTAL-STRUCTURE ; DEFICIENCY ; MUTATIONS ; METABOLISM ; BINDING |
| 资助项目 | the National Key Research and Development Program of China (2023YFC3605504)[2022YFC2703100] ; the National Key Research and Development Program of China (2023YFC3605504)[2023YFC3605504] ; National Key Research and Development Program of China[2021-I2M-1-003] ; Chinese Academy of Medical Sciences Initiative for Innovative Medicine[2022-PUMCH-D-002] ; Chinese Academy of Medical Sciences Initiative for Innovative Medicine[2022-PUMCH-B-098] ; National High-Level Hospital Clinical Research Funding[82225007] ; National High-Level Hospital Clinical Research Funding[92149305] ; National High-Level Hospital Clinical Research Funding[82030017] ; National Natural Science Foundation of China |
| WOS研究方向 | Life Sciences & Biomedicine - Other Topics ; Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:001469265900004 |
| 出版者 | NATURE PORTFOLIO |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/317473]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Chen, Houzao; Zhang, Shuyang; Luan, Xiaodong |
| 作者单位 | 1.Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China 2.Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Inst Clin Med, Beijing 100730, Peoples R China 3.Peking Union Med Coll & Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Cardiol, Beijing 100730, Peoples R China 4.Chinese Acad Med Sci & Peking Union Med Coll, Inst Basic Med Sci, Dept Biochem & Mol Biol, State Key Lab Med Mol Biol, Beijing 100005, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 6.Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China 7.Peking Union Med Coll & Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Rare Dis, Beijing 100730, Peoples R China |
| 推荐引用方式 GB/T 7714 | Su, Gengchen,Xu, Youwei,Chen, Binxian,et al. Structural and biochemical mechanism of short-chain enoyl-CoA hydratase (ECHS1) substrate recognition[J]. COMMUNICATIONS BIOLOGY,2025,8(1):12. |
| APA | Su, Gengchen.,Xu, Youwei.,Chen, Binxian.,Ju, Kaide.,Jin, Ye.,...&Luan, Xiaodong.(2025).Structural and biochemical mechanism of short-chain enoyl-CoA hydratase (ECHS1) substrate recognition.COMMUNICATIONS BIOLOGY,8(1),12. |
| MLA | Su, Gengchen,et al."Structural and biochemical mechanism of short-chain enoyl-CoA hydratase (ECHS1) substrate recognition".COMMUNICATIONS BIOLOGY 8.1(2025):12. |
入库方式： OAI收割
来源：上海药物研究所
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