Evidence map›Paper›PMID 40240482›Full record

ArticleCommunications biology2025

Structural and biochemical mechanism of short-chain enoyl-CoA hydratase (ECHS1) substrate recognition.

Gengchen Su, Youwei Xu, Binxian Chen, Kaide Ju, Ye Jin, Houzao Chen, Shuyang Zhang, Xiaodong Luan

Abstract read
In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
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  4. Review
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Gengchen SuDepartment of Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, 100730, Beijing, China.
Youwei XuThe CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 201203, Shanghai, China.ORCID http://orcid.org/0000-0001-8069-7511
Binxian ChenSchool of Medicine, Tsinghua University, 100084, Beijing, China.
Kaide JuSchool of Medicine, Tsinghua University, 100084, Beijing, China.
Ye JinDepartment of Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, 100730, Beijing, China.
Houzao ChenDepartment of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, 100005, Beijing, China. chenhouzao@ibms.cams.cn.ORCID http://orcid.org/0000-0001-6805-3182
Shuyang ZhangDepartment of Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, 100730, Beijing, China. shuyangzhang103@nrdrs.org.ORCID http://orcid.org/0000-0002-1532-0029
Xiaodong LuanDepartment of Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, 100730, Beijing, China. luanxiaodong@pumch.cn.ORCID http://orcid.org/0000-0002-1279-5432

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82030017National Natural Science Foundation of China (National Science Foundation of China) 82225007National Natural Science Foundation of China (National Science Foundation of China) 92149305
6 · The paper itself

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.

Indexed as

Enoyl-CoA HydrataseAcyl Coenzyme ACryoelectron MicroscopyHumansModels, MolecularProtein BindingProtein ConformationSubstrate SpecificityAcyl Coenzyme AECHS1 protein, humanEnoyl-CoA Hydratase

Identifiers

PMID40240482
PMCPMC12003839

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.