{"title":"贾第虫纤维素:序列和结构的生物信息学探索。","authors":"Francisco Alejandro Lagunas-Rangel","doi":"10.1007/s13353-024-00920-w","DOIUrl":null,"url":null,"abstract":"<p><p>Fibrillarin is a key nucleolar S-adenosyl-L-methionine (SAM)-dependent methyltransferase, highly conserved among species in both sequence and function. It is actively involved in numerous cellular processes, particularly in the early stages of pre-ribosomal RNA processing. Although a fibrillarin orthologue has been identified in Giardia, an intestinal protozoan parasite responsible for numerous infections worldwide, its functional and structural features in this parasite remain largely unexplored. In this study, bioinformatics tools were used to analyze the sequence and structure of Giardia fibrillarin to provide insights that could aid future experimental and therapeutic investigations. Taking advantage of the protein sequence of Giardia fibrillarin, multiple bioinformatics tools were employed to estimate its domains, nuclear and nucleolar localization signals (NLS and NoLS), post-translational modifications, phylogeny, and three-dimensional structure. The analysis revealed significant conservation of Giardia fibrillarin, showing close relationships with archaeal and parasitic amoeba orthologs. It retains essential features such as the SAM-dependent methyltransferase domain, a glycine- and arginine-rich domain, and both NLS and NoLS. While the core region of the protein is structurally conserved, the N-terminal region exhibits notable divergence. The potential for inhibition of Giardia fibrillarin by SAM competitors suggests that it could be a promising target for drug development, particularly for strains resistant to current treatments.</p>","PeriodicalId":14891,"journal":{"name":"Journal of Applied Genetics","volume":" ","pages":"241-248"},"PeriodicalIF":2.0000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761994/pdf/","citationCount":"0","resultStr":"{\"title\":\"Giardia fibrillarin: a bioinformatics exploration of sequence and structure.\",\"authors\":\"Francisco Alejandro Lagunas-Rangel\",\"doi\":\"10.1007/s13353-024-00920-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Fibrillarin is a key nucleolar S-adenosyl-L-methionine (SAM)-dependent methyltransferase, highly conserved among species in both sequence and function. It is actively involved in numerous cellular processes, particularly in the early stages of pre-ribosomal RNA processing. Although a fibrillarin orthologue has been identified in Giardia, an intestinal protozoan parasite responsible for numerous infections worldwide, its functional and structural features in this parasite remain largely unexplored. In this study, bioinformatics tools were used to analyze the sequence and structure of Giardia fibrillarin to provide insights that could aid future experimental and therapeutic investigations. Taking advantage of the protein sequence of Giardia fibrillarin, multiple bioinformatics tools were employed to estimate its domains, nuclear and nucleolar localization signals (NLS and NoLS), post-translational modifications, phylogeny, and three-dimensional structure. The analysis revealed significant conservation of Giardia fibrillarin, showing close relationships with archaeal and parasitic amoeba orthologs. It retains essential features such as the SAM-dependent methyltransferase domain, a glycine- and arginine-rich domain, and both NLS and NoLS. While the core region of the protein is structurally conserved, the N-terminal region exhibits notable divergence. The potential for inhibition of Giardia fibrillarin by SAM competitors suggests that it could be a promising target for drug development, particularly for strains resistant to current treatments.</p>\",\"PeriodicalId\":14891,\"journal\":{\"name\":\"Journal of Applied Genetics\",\"volume\":\" \",\"pages\":\"241-248\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2025-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761994/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Applied Genetics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1007/s13353-024-00920-w\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/11 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Applied Genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s13353-024-00920-w","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/11 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
Fibrillarin是一种关键的核仁S-腺苷-L-蛋氨酸(SAM)依赖性甲基转移酶,在序列和功能上都与不同物种高度一致。它积极参与许多细胞过程,尤其是核糖体前 RNA 处理的早期阶段。尽管在造成全球众多感染的肠道原生动物贾第虫(Giardia)中发现了纤维素的直向同源物,但该寄生虫中纤维素的功能和结构特征在很大程度上仍未得到探索。本研究利用生物信息学工具分析了贾第鞭毛虫纤毛蛋白的序列和结构,以提供有助于未来实验和治疗研究的见解。利用贾第虫纤毛虫蛋白序列的优势,多种生物信息学工具被用来估算其结构域、核定位信号和核极定位信号(NLS 和 NoLS)、翻译后修饰、系统发育和三维结构。分析结果表明,贾第虫纤维素具有明显的保守性,与古生菌和寄生变形虫的直向同源物关系密切。它保留了一些基本特征,如依赖于 SAM 的甲基转移酶结构域、富含甘氨酸和精氨酸的结构域以及 NLS 和 NoLS。虽然该蛋白的核心区域在结构上是保守的,但 N 端区域却表现出明显的差异。SAM 竞争对手对贾第虫纤维素的潜在抑制作用表明,它可能是一个很有前景的药物开发目标,尤其是对目前治疗方法有抗药性的菌株。
Giardia fibrillarin: a bioinformatics exploration of sequence and structure.
Fibrillarin is a key nucleolar S-adenosyl-L-methionine (SAM)-dependent methyltransferase, highly conserved among species in both sequence and function. It is actively involved in numerous cellular processes, particularly in the early stages of pre-ribosomal RNA processing. Although a fibrillarin orthologue has been identified in Giardia, an intestinal protozoan parasite responsible for numerous infections worldwide, its functional and structural features in this parasite remain largely unexplored. In this study, bioinformatics tools were used to analyze the sequence and structure of Giardia fibrillarin to provide insights that could aid future experimental and therapeutic investigations. Taking advantage of the protein sequence of Giardia fibrillarin, multiple bioinformatics tools were employed to estimate its domains, nuclear and nucleolar localization signals (NLS and NoLS), post-translational modifications, phylogeny, and three-dimensional structure. The analysis revealed significant conservation of Giardia fibrillarin, showing close relationships with archaeal and parasitic amoeba orthologs. It retains essential features such as the SAM-dependent methyltransferase domain, a glycine- and arginine-rich domain, and both NLS and NoLS. While the core region of the protein is structurally conserved, the N-terminal region exhibits notable divergence. The potential for inhibition of Giardia fibrillarin by SAM competitors suggests that it could be a promising target for drug development, particularly for strains resistant to current treatments.
期刊介绍:
The Journal of Applied Genetics is an international journal on genetics and genomics. It publishes peer-reviewed original papers, short communications (including case reports) and review articles focused on the research of applicative aspects of plant, human, animal and microbial genetics and genomics.