Novel and unique domains in aminoacyl-tRNA synthetases from human fungal pathogens Aspergillus niger, Candida albicans and Cryptococcus neoformans.
Novel and unique domains in aminoacyl-tRNA synthetases from human fungal pathogens Aspergillus niger, Candida albicans and Cryptococcus neoformans.
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DOI：
10.1186/1471-2164-15-1069
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发表时间：
2014-12-05
期刊：
影响因子：
4.4
通讯作者：
Sharma A
中科院分区：
文献类型：
--
作者：
Datt M;Sharma A
某些种类的真菌会导致严重的人类疾病，特别是对免疫功能低下的人。机会性真菌感染是导致死亡的主要原因，是一个新的挑战，需要开发新的有效的治疗方法。氨基酰-tRNA合成酶(AARs)是细胞蛋白质翻译机制中不可缺少的组成部分，可作为发现新型抗真菌药物的靶点。AARS作为致病微生物潜在药物靶点的验证促使我们调查了AARS在感染人类的三种真菌--黑曲霉、白色念珠菌和新生葡萄球菌--中的基因组分布。为了寻找这些真菌基因组中的同源基因，我们建立了AARS及其相关蛋白质的隐马尔可夫模型。在这里，我们提供了3个真菌基因组AARS及其相关蛋白的详细和全面的注释。我们描述了预测的局部化、子域架构和这些AARS中不寻常的基序的流行。一些真菌AARS具有未知功能的独特结构域附件，例如黑曲霉AsxRS和新生葡萄球菌TyrRS具有人类同源基因所没有的额外结构域。真菌AARs与人类同源物的详细比较表明，可以利用的关键差异可以用于特定的药物靶向。我们的分类和结构分析为实验解剖真菌AARS提供了全面的基础，这可能使新的抗真菌药物的开发成为可能。本文的在线版本(DOI：10.1186/1471-2164-15-1069)包含补充材料，授权用户可以使用。
Some species of fungi can cause serious human diseases, particularly to immuno-compromised individuals. Opportunistic fungal infections are a leading cause of mortality, and present an emerging challenge that requires development of new and effective therapeutics. Aminoacyl-tRNA synthetases (aaRSs) are indispensable components of cellular protein translation machinery and can be targeted for discovery of novel anti-fungal agents. Validation of aaRSs as potential drug targets in pathogenic microbes prompted us to investigate the genomic distribution of aaRSs within three fungi that infect humans – A. niger, C. albicans and C. neoformans. Hidden Markov Models were built for aaRSs and related proteins to search for homologues in these fungal genomes. Here, we provide a detailed and comprehensive annotation for 3 fungal genome aaRSs and their associated proteins. We delineate predicted localizations, subdomain architectures and prevalence of unusual motifs within these aaRSs. Several fungal aaRSs have unique domain appendages of unknown function e.g. A. niger AsxRS and C. neoformans TyrRS have additional domains that are absent from human homologs. Detailed comparisons of fungal aaRSs with human homologs suggest key differences that could be exploited for specific drug targeting. Our cataloging and structural analyses provide a comprehensive foundation for experimentally dissecting fungal aaRSs that may enable development of new anti-fungal agents. The online version of this article (doi:10.1186/1471-2164-15-1069) contains supplementary material, which is available to authorized users.
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DOI：
10.1126/science.1174343
发表时间：
2009-08-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Guo M;Chong YE;Beebe K;Shapiro R;Yang XL;Schimmel P
通讯作者：
Schimmel P
影响因子：
4.4
作者：
Bhatt TK;Kapil C;Khan S;Jairajpuri MA;Sharma V;Santoni D;Silvestrini F;Pizzi E;Sharma A
通讯作者：
Sharma A
影响因子：
4.8
作者：
Ginder, Nathaniel D.;Binkowski, Daniel J.;Honzatko, Richard B.
通讯作者：
Honzatko, Richard B.
DOI：
10.1073/pnas.1011560108
发表时间：
2011-01-25
影响因子：
11.1
作者：
Istvan, Eva S.;Dharia, Neekesh V.;Goldberg, Daniel E.
通讯作者：
Goldberg, Daniel E.
影响因子：
4.4
作者：
Gowri, V. S.;Ghosh, Indira;Madhubala, Rentala
通讯作者：
Madhubala, Rentala