人纤溶酶原与烟曲霉烯醇化酶复合物的结构模型

Stephanie Nguyen, Blagojce Jovcevski, J. Truong, T. Pukala, J. Bruning
{"title":"人纤溶酶原与烟曲霉烯醇化酶复合物的结构模型","authors":"Stephanie Nguyen, Blagojce Jovcevski, J. Truong, T. Pukala, J. Bruning","doi":"10.1002/prot.26331","DOIUrl":null,"url":null,"abstract":"The metabolic enzyme, enolase, plays a crucial role in the cytoplasm where it maintains cellular energy production within the process of glycolysis. The main role of enolase in glycolysis is to convert 2‐phosphoglycerate to phosphoenolpyruvate; however, enolase can fulfill roles that deviate from this function. In pathogenic bacteria and fungi, enolase is also located on the cell surface where it functions as a virulence factor. Surface‐expressed enolase is a receptor for human plasma proteins, including plasminogen, and this interaction facilitates nutrient acquisition and tissue invasion. A novel approach to developing antifungal drugs is to inhibit the formation of this complex. To better understand the structure of enolase and the interactions that may govern complex formation, we have solved the first X‐ray crystal structure of enolase from Aspergillus fumigatus (2.0 Å) and have shown that it preferentially adopts a dimeric quaternary structure using native mass spectrometry. Two additional X‐ray crystal structures of A. fumigatus enolase bound to the endogenous substrate 2‐phosphoglycerate and product phosphoenolpyruvate were determined and kinetic characterization was carried out to better understand the details of its canonical function. From these data, we have produced a model of the A. fumigatus enolase and human plasminogen complex to provide structural insights into the mechanisms of virulence and aid future development of small molecules or peptidomimetics for antifungal drug design.","PeriodicalId":20789,"journal":{"name":"Proteins: Structure","volume":"143 1","pages":"1509 - 1520"},"PeriodicalIF":0.0000,"publicationDate":"2022-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A structural model of the human plasminogen and Aspergillus fumigatus enolase complex\",\"authors\":\"Stephanie Nguyen, Blagojce Jovcevski, J. Truong, T. Pukala, J. Bruning\",\"doi\":\"10.1002/prot.26331\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"The metabolic enzyme, enolase, plays a crucial role in the cytoplasm where it maintains cellular energy production within the process of glycolysis. The main role of enolase in glycolysis is to convert 2‐phosphoglycerate to phosphoenolpyruvate; however, enolase can fulfill roles that deviate from this function. In pathogenic bacteria and fungi, enolase is also located on the cell surface where it functions as a virulence factor. Surface‐expressed enolase is a receptor for human plasma proteins, including plasminogen, and this interaction facilitates nutrient acquisition and tissue invasion. A novel approach to developing antifungal drugs is to inhibit the formation of this complex. To better understand the structure of enolase and the interactions that may govern complex formation, we have solved the first X‐ray crystal structure of enolase from Aspergillus fumigatus (2.0 Å) and have shown that it preferentially adopts a dimeric quaternary structure using native mass spectrometry. Two additional X‐ray crystal structures of A. fumigatus enolase bound to the endogenous substrate 2‐phosphoglycerate and product phosphoenolpyruvate were determined and kinetic characterization was carried out to better understand the details of its canonical function. From these data, we have produced a model of the A. fumigatus enolase and human plasminogen complex to provide structural insights into the mechanisms of virulence and aid future development of small molecules or peptidomimetics for antifungal drug design.\",\"PeriodicalId\":20789,\"journal\":{\"name\":\"Proteins: Structure\",\"volume\":\"143 1\",\"pages\":\"1509 - 1520\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-03-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Proteins: Structure\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1002/prot.26331\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Proteins: Structure","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/prot.26331","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

代谢酶烯醇化酶在细胞质中起着至关重要的作用,它在糖酵解过程中维持细胞能量的产生。烯醇化酶在糖酵解中的主要作用是将2 -磷酸甘油酸转化为磷酸烯醇丙酮酸;然而,烯醇化酶可以完成偏离此功能的角色。在致病菌和真菌中,烯醇化酶也位于细胞表面,在那里它起着毒力因子的作用。表面表达的烯醇化酶是人血浆蛋白(包括纤溶酶原)的受体,这种相互作用促进了营养获取和组织入侵。一种开发抗真菌药物的新方法是抑制这种复合物的形成。为了更好地了解烯醇化酶的结构和可能控制复合物形成的相互作用,我们已经解决了烟曲霉烯醇化酶(2.0 Å)的第一个X射线晶体结构,并表明它优先采用二聚体四元结构。测定了烟曲霉烯醇化酶与内源性底物2 -磷酸甘油酸酯和产物磷酸烯醇丙酮酸酯结合的另外两个X射线晶体结构,并进行了动力学表征,以更好地了解其典型功能的细节。根据这些数据,我们建立了烟曲霉烯醇化酶和人纤溶酶原复合物的模型,为毒力机制提供结构见解,并有助于未来小分子或拟肽物的开发,用于抗真菌药物设计。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A structural model of the human plasminogen and Aspergillus fumigatus enolase complex
The metabolic enzyme, enolase, plays a crucial role in the cytoplasm where it maintains cellular energy production within the process of glycolysis. The main role of enolase in glycolysis is to convert 2‐phosphoglycerate to phosphoenolpyruvate; however, enolase can fulfill roles that deviate from this function. In pathogenic bacteria and fungi, enolase is also located on the cell surface where it functions as a virulence factor. Surface‐expressed enolase is a receptor for human plasma proteins, including plasminogen, and this interaction facilitates nutrient acquisition and tissue invasion. A novel approach to developing antifungal drugs is to inhibit the formation of this complex. To better understand the structure of enolase and the interactions that may govern complex formation, we have solved the first X‐ray crystal structure of enolase from Aspergillus fumigatus (2.0 Å) and have shown that it preferentially adopts a dimeric quaternary structure using native mass spectrometry. Two additional X‐ray crystal structures of A. fumigatus enolase bound to the endogenous substrate 2‐phosphoglycerate and product phosphoenolpyruvate were determined and kinetic characterization was carried out to better understand the details of its canonical function. From these data, we have produced a model of the A. fumigatus enolase and human plasminogen complex to provide structural insights into the mechanisms of virulence and aid future development of small molecules or peptidomimetics for antifungal drug design.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信