更新于：2024-05-01

ECHS1

enoyl-CoA hydratase, short chain 1

更新于：2024-05-01

基本信息

别名

ECHS1、Enoyl-CoA hydratase 1、Enoyl-CoA hydratase, mitochondrial

+ [5]

简介

Converts unsaturated trans-2-enoyl-CoA species ((2E)-enoyl-CoA) to the corresponding (3S)-3hydroxyacyl-CoA species through addition of a water molecule to the double bond (PubMed:25125611, PubMed:26251176). Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:26251176). Has high substrate specificity for crotonyl-CoA ((2E)-butenoyl-CoA) and moderate specificity for acryloyl-CoA, 3-methylcrotonyl-CoA (3-methyl-(2E)-butenoyl-CoA) and methacrylyl-CoA ((2E)-2-methylpropenoyl-CoA) (PubMed:26251176). Can bind tiglyl-CoA (2-methylcrotonoyl-CoA), but hydrates only a small amount of this substrate (PubMed:26251176). Plays a key role in the beta-oxidation spiral of short- and medium-chain fatty acid oxidation (PubMed:25125611, PubMed:26251176). At a lower rate than the hydratase reaction, catalyzes the isomerase reaction of trans-3-enoyl-CoA species (such as (3E)-hexenoyl-CoA) to trans-2-enoyl-CoA species (such as (2E)-hexenoyl-CoA), which are subsequently hydrated to 3(S)-3-hydroxyacyl-CoA species (such as (3S)-hydroxyhexanoyl-CoA) (By similarity).

关联

100 项与 ECHS1 相关的临床结果

登录后查看更多信息

100 项与 ECHS1 相关的转化医学

登录后查看更多信息

0 项与 ECHS1 相关的专利（医药）

登录后查看更多信息

755

项与 ECHS1 相关的文献（医药）

2024-02-16·Metabolic brain disease

Molecular and in silico investigation of a novel ECHS1 gene mutation in a consanguine family with short-chain enoyl-CoA hydratase deficiency and Mt-DNA depletion: effect on trimer assembly and catalytic activity.

Article

作者: Marwa Maalej ; Lamia Sfaihi ; Olfa-Alila Fersi ; Boudour Khabou ; Marwa Ammar ; Rahma Felhi ; Marwa Kharrat ; Jihen Chouchen ; Thouraya Kammoun ; Abdelaziz Tlili ; Faiza Fakhfakh

Short-chain enoyl-CoA hydratase deficiency (ECHS1D) is a rare congenital metabolic disorder that follows an autosomal recessive inheritance pattern. It is caused by mutations in the ECHS1 gene, which encodes a mitochondrial enzyme involved in the second step of mitochondrial β-oxidation of fatty acids. The main characteristics of the disease are severe developmental delay, regression, seizures, neurodegeneration, high blood lactate, and a brain MRI pattern consistent with Leigh syndrome. Here, we report three patients belonging to a consanguineous family who presented with mitochondrial encephalomyopathy. Whole-exome sequencing revealed a new homozygous mutation c.619G > A (p.Gly207Ser) at the last nucleotide position in exon 5 of the ECHS1 gene. Experimental analysis showed that normal ECHS1 pre-mRNA splicing occurred in all patients compared to controls. Furthermore, three-dimensional models of wild-type and mutant echs1 proteins revealed changes in catalytic site interactions, conformational changes, and intramolecular interactions, potentially disrupting echs1 protein trimerization and affecting its function. Additionally, the quantification of mtDNA copy number variation in blood leukocytes showed severe mtDNA depletion in all probands.

2024-01-06·Environmental microbiology

Metagenomic and proteomic insights into the self-adaptive cell surface hydrophobicity of Sphingomonas sp. strain PAH02 reducing the migration of cadmium-phenanthrene co-pollutant in rice.

Article

作者: Shengwei Yi ; Zhongnan Zhu ; Feng Li ; Lizhong Zhu ; Chen Wu ; Fei Ge ; Xionghui Ji ; Jiang Tian

Cell surface hydrophobicity (CSH) dominates the interactions between rhizobacteria and pollutants at the soil-water interface, which is critical for understanding the dissipation of pollutants in the rhizosphere microzone of rice. Herein, we explored the effects of self-adaptive CSH of Sphingomonas sp. strain PAH02 on the translocation and biotransformation behaviour of cadmium-phenanthrene (Cd-Phe) co-pollutant in rice and rhizosphere microbiome. We evidenced that strain PAH02 reduced the adsorption of Cd-Phe co-pollutant on the rice root surface while enhancing the degradation of Phe and adsorption of Cd via its self-adaptive CSH in the hydroponic experiment. The significant upregulation of key protein expression levels such as MerR, ARHDs and enoyl-CoA hydratase/isomerase, ensures self-adaptive CSH to cope with the stress of Cd-Phe co-pollutant. Consistently, the bioaugmentation of strain PAH02 promoted the formation of core microbiota in the rhizosphere soil of rice (Oryza sativa L.), such as Bradyrhizobium and Streptomyces and induced gene enrichment of CusA and PobA that are strongly associated with pollutant transformation. Consequently, the contents of Cd and Phe in rice grains at maturity decreased by 17.2% ± 0.2% and 65.7% ± 0.3%, respectively, after the bioaugmentation of strain PAH02. These findings present new opportunities for the implementation of rhizosphere bioremediation strategies of co-contaminants in paddy fields.

2024-01-01·Journal of Cancer

Expression and clinical significance of ECHS1 in gastric cancer.

Article

作者: Ting Lu ; Liang Sun ; Qingmin Fan ; Junchen Yan ; Dan Zhao ; Chunfang Xu ; Fenglin Dong

Background: Gastric cancer (GC), as one of the most common malignant tumors and the 3rd primary cause of death by cancer globally, poses a great threat to public health. Despite many advancements have been achieved in current treatment avenues for GC, the 5-year survival rates of GC patients remain substandard. Short-chain enoyl-CoA hydratase (ECHS1) exerts pro- or anti-cancer activities in different cancer backgrounds. However, its clinical significance and biological role in GC remain vague and need further investigation. Methods: The expression of ECHS1 in GC tumors and adjacent normal tissues was examined using the GEPIA platform and clinical samples. The effects of ECHS1 on GC cell proliferation and migration were evaluated using colony formation and transwell migration assays. Results: ECHS1 was upregulated in GC tumor tissues in both mRNA and protein levels and increased ECHS1 was markedly linked with tumor location, depth of tumor invasion, lymph node metastasis (LNM), and tumor-node-metastasis (TNM) stage of GC patients. High ECHS1 expression was also linked with a shorter overal survival (OS), first progression (FP) and post progression survival (PPS). Further subgroup analysis showed that OS was significantly shorter in GC patients with high ECHS1 expression compared to those with low ECHS1 expression belonging to tumors with T3 stage, N2 stage or in instestinal Lauren subgroup. In addition, cytological experiments showed that there was higher ECHS1 expression in GC cell lines compared to the normal gastric epithelium (GES-1) cells, and ECHS1 can promote GC cell proliferation and migration in vitro. Conclusion: ECHS1 plays an oncogenic role in GC and might be a promising therapeutic target for GC.

项与 ECHS1 相关的新闻（医药）

2024-02-15

·医药魔方Pro

中国科学家最新Nature：抗癌新靶点——FGA

原发性肝癌的致死率在全球所有癌症中高居第三，肝细胞癌（hepatocellular carcinoma, HCC）为其主要亚型，约占其所有病例的80%以上。全球每年肝癌新发病例超过一半发生在中国，且患者预后普遍较差，我国肝细胞癌患者五年总体生存率仅约为10%。肝细胞癌病因复杂，其中HCV（hepatitis C virus）感染在日本人群最为常见，酒精、非酒精性脂肪性肝炎（NASH）及代谢紊乱在西方人群中占比较大，而HBV（hepatitis B virus）慢性感染和黄曲霉毒素（aflatoxin）等致癌物暴露是中国肝癌人群的主要致病因素。既往的国际泛癌全基因组研究计划（Pan-Cancer Analysis of Whole Genomes, PCAWG）和美国癌症基因组研究计划（The Cancer Genome Atlas, TCGA）虽然包含了对肝癌全基因组特征的研究，但其样本主要为日本和西方人群，其结果不能全面反映中国人群肝癌的基因组特征。另一方面，这些研究采用了相对较浅的测序深度（~30-40X），限制了其对全基因组层面亚克隆结构的深度解析。鉴于不同区域、不同人群肝癌致病因素的巨大差异，迫切需要开展一项大规模、高深度的中国肝癌人群全基因特征分析，为开发适用于中国肝癌人群的诊断和治疗方案提供依据。来源：Nature2月14日，北京大学生物医学前沿创新中心/北京未来基因诊断高精尖创新中心白凡教授课题组联合海军军医大学王红阳院士/陈磊研究员课题组、杜克-新加坡国立大学医学院Steven G. Rozen教授课题组以及贝瑞基因吴琳博士团队合作在Nature在线发表了题为 Deep whole-genome analysis of 494 hepatocellular carcinomas的最新研究成果，完成了中国人群肝细胞癌全基因组深度特征分析（Chinese Liver Cancer Atlas, CLCA）。具体来说，该研究对494例来自中国不同地区的肝细胞癌患者肿瘤组织进行了高深度的全基因组测序（平均120x），深入分析了编码区和非编码区的驱动基因、突变印记、拷贝数变异、聚集式变异事件（clustered alteration：chromothripsis, chromoplexy和kataegis）、染色体外环状DNA（extrachromosomal circular DNA, ecDNA）以及突变演进规律等特征，揭示了以HBV相关肝细胞癌为主的全基因组变异景观，为深入理解中国人群肝细胞癌的演进机理提供了重要的线索（图1）。图1. CLCA研究方案与中国人群肝癌驱动基因全景与PCAWG-HCC队列相比，该研究的CLCA-HCC队列具有更高的HBV感染率（94.5%）、Edmondson-Steiner III-IV级分期（85.6%）和更低的HCV感染率（2.6%）、吸烟史（36.8%）及饮酒史（26.7%）占比，提示CLCA-HCC队列具有明显不同的流行病学和临床病理特征。研究首先综合多种算法，鉴定出大量新的肝癌潜在驱动事件，包括6个新编码驱动事件（FGA, HNF1A, PRDM11, CDKN1B, BMP5和ECHS1）和28个新非编码驱动事件（完整列表见原文）。值得注意的是，研究所发现的31个非编码驱动事件中仅有3个被报道过，同时多个基因都与肝脏代谢通路密切相关，该结果提示现有研究对肝癌非编码区的探究仍十分有限。通过亚克隆富集分析，研究者揭示62.5%的非编码驱动事件富集在亚克隆区域，说明非编码驱动事件并非只发生在肝癌发生早期，而是广泛参与了肝癌的亚克隆演化。其次，在PCAWG已报道的81种突变印记的基础上，本研究首次鉴定了5种新的突变印记，包括2种双碱基替换（doublet-base substitution：DBS_H1, DBS_H2）、2种插入缺失（insertion-and-deletion：ID_H3, ID_H8）和1种单碱基替换（single-base substitution signature：SBS_H8）（图2）。值得注意的是，ID_H8与黄曲霉毒素暴露相关，而DBS_H2和ID_H3则与马兜铃酸（aristolochic acid, AA）暴露相关，这些新突变印记是单碱基替换印记的重要补充。更重要的是，研究人员通过数据分析及细胞系实验共同证实SBS_H8是一种不同于马兜铃酸突变印记（SBS_22）的新型单碱基替换印记，提示其相关致病因素并非马兜铃酸。与PCAWG-HCC队列相比（0.31%），CLCA-HCC队列中SBS_H8高度富集（57.1%），并与Wnt/β-catenin信号通路的突变和预后不良密切相关。同时亚克隆富集分析揭示SBS_H8显著富集于主克隆突变中，提示该突变特征在中国人群肝细胞癌的早期演进过程中发挥重要作用。图2. 中国人群肝癌突变印记特征随后，研究还详细描绘了CLCA队列中不同类型的基因组变异事件，包括拷贝数变异、结构变异、HBV整合、ecDNA和三种类型的聚集式变异事件（Chromothripsis, chromoplexy和kataegis）（图3）。有趣的是，CLCA-HCC队列中ecDNA比例（27.3%）显著高于PCAWG-HCC队列（13.1%），同时ecDNA中整合的癌基因谱也具有独特性。虽然肝癌中HBV整合事件早有报道，但其如何整合到基因组中仍不十分清楚。该研究发现HBV可以与宿主基因组形成ecDNA，与线性DNA相比，这种HBV-oncogene-ecDNA的整合形式显著提高了临近驱动基因的拷贝数和表达水平，提示ecDNA的扩增可能在HBV相关肝癌中扮演着重要角色。Chromothripsis, chromoplexy 和kataegis等聚集式变异事件通常被认为发生在早期，也是肿瘤截断式演化（punctuated evolution）的重要证据，该研究发现这些聚集式变异事件同样存在于亚克隆事件中，提示这些基因组灾难性事件也有可能发生在肿瘤进展后期，其结果更支持肿瘤的截断-渐进双相演化模型。这一结果打破了既往对肿瘤演化规律的刻板认知，丰富了对肝癌演化模式的理解。图3. 中国人群集群突变事件特征最后，研究者还选取了三个新鉴定的潜在驱动事件（PPP1R12B, KCNJ12, FGA）进行详细功能验证，综合CRISPR定点突变及多个细胞系敲降/敲除实验，发现上述基因的突变足以导致基因表达水平的显著变化，并参与调控肝细胞癌的多种恶性表型，这些结果证实基于数据分析发现的新驱动事件的有效性。深入功能机制探究进一步揭示，潜在驱动基因FGA（编码纤维蛋白原α链，被同时鉴定为编码驱动事件和非编码驱动事件）通过负向调控TYK2-STAT3-IL6信号通路影响多种肝癌细胞的恶性表型，提示FGA及其相关信号通路有望成为肝细胞癌潜在的干预和治疗靶点（图4）。图4. FGA基因的功能机制研究总结来说，这项研究所建立的中国肝癌人群基因组变异特征全景图谱，为深入理解不同病因肝癌的发生和演进分子机制、开发全新的个体化靶向药物提供了宝贵资源，有助于提升中国肝癌的临床精准诊疗水平，造福广大肝癌患者。备注：本文转载自“北京大学生物医学前沿创新中心”，原标题：Nature | 白凡课题组与王红阳院士团队联合揭示中国人群肝癌全基因组变异及演化特征。参考资料：[1]https://www.nature.com/articles/s41586-024-07054-3推荐阅读标新生物杨小宝：突破制药边界，蛋白降解剂前景无限本导基因蔡宇伽：基因编辑疗法的“终极目标”——体内编辑圣诺医药陆阳：RNAi疗法逆势而上，实体瘤是下一个高地滨会生物刘滨磊：癌症免疫疗法下一张王牌——溶瘤病毒沙砾生物刘雅容：TIL细胞疗法突破不断，2024将是「关键年」霍德生物范靖：iPSC细胞疗法强势崛起，多种疾病治疗有望「开花结果」智核生物须涛：核药赛道火爆，2.0时代机会无限医药魔方Pro新靶点新技术新疗法商务合作：13502093012媒体合作：15895423126