更新于：2024-09-19

NAA50

更新于：2024-09-19

基本信息

别名

FLJ13194、hNaa50p、hNAT5

+ [13]

简介

N-alpha-acetyltransferase that acetylates the N-terminus of proteins that retain their initiating methionine (PubMed:19744929, PubMed:22311970, PubMed:21900231, PubMed:27484799). Has a broad substrate specificity: able to acetylate the initiator methionine of most peptides, except for those with a proline in second position (PubMed:27484799). Also displays N-epsilon-acetyltransferase activity by mediating acetylation of the side chain of specific lysines on proteins (PubMed:19744929). Autoacetylates in vivo (PubMed:19744929). The relevance of N-epsilon-acetyltransferase activity is however unclear: able to acetylate H4 in vitro, but this result has not been confirmed in vivo (PubMed:19744929). Component of N-alpha-acetyltransferase complexes containing NAA10 and NAA15, which has N-alpha-acetyltransferase activity (PubMed:16507339, PubMed:29754825, PubMed:27484799, PubMed:32042062). Does not influence the acetyltransferase activity of NAA10 (PubMed:16507339, PubMed:27484799). However, it negatively regulates the N-alpha-acetyltransferase activity of the N-terminal acetyltransferase A complex (also called the NatA complex) (PubMed:32042062). The multiprotein complexes probably constitute the major contributor for N-terminal acetylation at the ribosome exit tunnel, with NAA10 acetylating all amino termini that are devoid of methionine and NAA50 acetylating other peptides (PubMed:16507339, PubMed:27484799). Required for sister chromatid cohesion during mitosis by promoting binding of CDCA5/sororin to cohesin: may act by counteracting the function of NAA10 (PubMed:17502424, PubMed:27422821).

关联

100 项与 NAA50 相关的临床结果

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100 项与 NAA50 相关的转化医学

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0 项与 NAA50 相关的专利（医药）

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156

项与 NAA50 相关的文献（医药）

2024-07-31·Plant Physiology

Nα-acetyltransferase NAA50 mediates plant immunity independent of the Nα-acetyltransferase A complex

Article

作者: Poschet, Gernot ; Sticht, Carsten ; Miklánková, Pavlina ; Huber, Monika ; Pożoga, Marlena ; Hell, Rüdiger ; Finkemeier, Iris ; Eirich, Jürgen ; De La Torre, Carolina ; Bradic, Fabian ; Ruppert, Thomas ; Wu, Zhongshou ; Weidenhausen, Jonas ; Armbruster, Laura ; Sinning, Irmgard ; Merker, Sabine ; Wirtz, Markus ; Thulasi Devendrakumar, Karen ; Li, Xin

AbstractIn humans and plants, 40% of the proteome is cotranslationally acetylated at the N-terminus by a single Nα-acetyltransferase (Nat) termed NatA. The core NatA complex is comprised of the catalytic subunit Nα-acetyltransferase 10 (NAA10) and the ribosome-anchoring subunit NAA15. The regulatory subunit Huntingtin Yeast Partner K (HYPK) and the acetyltransferase NAA50 join this complex in humans. Even though both are conserved in Arabidopsis (Arabidopsis thaliana), only AtHYPK is known to interact with AtNatA. Here we uncover the AtNAA50 interactome and provide evidence for the association of AtNAA50 with NatA at ribosomes. In agreement with the latter, a split-luciferase approach demonstrated close proximity of AtNAA50 and AtNatA in planta. Despite their interaction, AtNatA/HYPK and AtNAA50 exerted different functions in vivo. Unlike NatA/HYPK, AtNAA50 did not modulate drought tolerance or promote protein stability. Instead, transcriptome and proteome analyses of a novel AtNAA50-depleted mutant (amiNAA50) implied that AtNAA50 negatively regulates plant immunity. Indeed, amiNAA50 plants exhibited enhanced resistance to oomycetes and bacterial pathogens. In contrast to what was observed in NatA-depleted mutants, this resistance was independent of an accumulation of salicylic acid prior to pathogen exposure. Our study dissects the in vivo function of the NatA interactors HYPK and NAA50 and uncovers NatA-independent roles for NAA50 in plants.

2024-06-01·Morphologie

Anatomical variations in the course of spinal accessory nerve in the neck triangles: A descriptive study

Article

作者: Banu, J ; Hottigoudar, S Y ; Dhakshnamoorthy, N ; Sakthivel, S

BACKGROUNDSpinal Accessory Nerve (SAN), which innervates the sternocleidomastoid (SCM) and trapezius muscles, is closely related to the internal jugular vein (IJV) in the anterior triangle of the neck and passes superficially in the posterior triangle. Injury to SAN is a major complication of level II neck dissection, leading to shoulder syndrome. The present study aims to assess the course and its relation to the SCM muscle and IJV in the Tamil ethnolinguistic groups in South India.METHODS AND MATERIALSThe anterior and posterior triangles of the neck were dissected in 28 formalin-fixed adult cadavers. The course of the SAN and the entry and exit points of SAN along the SCM muscle were assessed using the mastoid process as the reference. Recorded data was analyzed using SPSS software.RESULTSThe SAN was anteriorly related to the IJV in 58.73%, posteriorly in 37.5%, and pierced through the IJV in 3.57% of the specimens. The entry and exit points of SAN from the mastoid process were 37.86±7.26mm and 48.55±8.22mm, respectively. In 86.67% of the cases, the SAN traversed through the SCM muscle, and in 13.33%, it was deep to the SCM.CONCLUSIONThe present study reports that the SAN is variable in its course, and relation to SCM and IJV. Knowledge about the variant anatomy of the SAN in the triangles of the neck is important and it aids surgeons to prevent iatrogenic injuries to SAN or IJV and enhance surgical safety in neck procedures.

2024-02-21·Current Computer-Aided Drug Design

Exploring the Mechanisms of Sanguinarine in the Treatment of Osteoporosis by Integrating Network Pharmacology Analysis and Deep Learning Technology

Article

作者: Zhou, Daoqing ; Yao, Zhicheng ; Tang, Yonghong ; Zeng, Yuqing ; Gan, Fengping

Background::Sanguinarine (SAN) has been reported to have antioxidant, antiinflammatory, and antimicrobial activities with potential for the treatment of osteoporosis (OP).Objective::This work purposed to unravel the molecular mechanisms of SAN in the treatment of OP.Methods::OP-related genes and SAN-related targets were predicted from public databases. Differential expression analysis and VennDiagram were adopted to detect SAN-related targets against OP. Protein-protein interaction (PPI) network was served for core target identification. Molecular docking and DeepPurpose algorithm were further adopted to investigate the binding ability between core targets and SAN. Gene pathway scoring of these targets was calculated utilizing gene set variation analysis (GSVA). Finally, we explored the effect of SAN on the expressions of core targets in preosteoblastic MC3T3-E1 cells.Results::A total of 21 candidate targets of SAN against OP were acquired. Furthermore, six core targets were identified, among which CASP3, CTNNB1, and ERBB2 were remarkably differentially expressed in OP and healthy individuals. The binding energies of SAN with CASP3, CTNNB1, and ERBB2 were -6, -6.731, and -7.162 kcal/mol, respectively. Moreover, the GSVA scores of the Wnt/calcium signaling pathway were significantly lower in OP cases than in healthy individuals. In addition, the expression of CASP3 was positively associated with Wnt/calcium signaling pathway. CASP3 and ERBB2 were significantly lower expressed in SAN group than in DMSO group, whereas the expression of CTNNB1 was in contrast.Conclusion::CASP3, CTNNB1, and ERBB2 emerge as potential targets of SAN in OP prevention and treatment.

项与 NAA50 相关的新闻（医药）

2024-05-30

·药时代

创新药春暖花开

如何打造更具想象力的源头创新药？创新药的春天到底在哪？未解之谜或将解开。据报道，目前GSK正在进行包括GSK-2256294、GSK-2982772和GSK-3145095在内的多款基于DEL技术开发的药物的II期临床。值得一提的是，GSK-2982772临床适应症开发为银屑病、类风湿性关节炎、溃疡性结肠炎等自免疾病，如若最终获批上市，有望成为自免领域的下一颗新星。助力创新药从0到1，一款全球排名前20的药企几乎都布局了的技术，DEL是何方神圣？DEL那些事DEL，是DNA编码化合物库（DNA encoded compound library）的简称。相较于传统的高通量筛选，DEL化合物文库的容量更大、文库化合物具有标签属性、可以同时对多个或同一靶标蛋白的多个条件进行筛选、筛选效率提升、单化合物的费用显著降低。图1 DEL技术在药物发现开发时间轴的位置图片来源：Acta Pharmaceutica SinicaB.doi.org/10.1016/j.apsb.2024.04.006DEL技术对应的各个环节，主要有1）DNA编码化合物库的构建；2）基于库进行的亲和筛选工作；3）筛选结果的解码与解析；4）定向合成与再验证。库的建立：通常使用组合化学经典的“均分-混合-均分”策略来构建上亿级别的DEL文库，构建方法主要包括DNA记录法、DNA模板法、编码自组装化学法、DNA链接法等，方法虽不同但目标均指向构建上亿级别的化合物库，且每个化合物都与一个确切的DNA标签共价结合对应。亲和筛选：在传统筛选方法的基础上，目前主要扩增为“固化靶点蛋白与化合物库的亲和筛选”、“非固化靶点蛋白与化合物库的亲和筛选”、“固化靶点蛋白与固化化合物库的亲和筛选”、“基于细胞的筛选”等。解码解析：通常会进行1-3轮的亲和筛选，并基于扩增、高通量测序，以及多种模型与算法的结合，来提升解码解析的准确性。定向合成与验证：将构建文库时用的相同合成路线和方法进行ON-DNA的重合成，并进一步进行ON-DNA的亲和质谱分析。再，将目标化合物（苗头）进行生物化学测试、结构优化等工作，逐渐转移到药物化学方向，最终得到候选药物。图2 DEL库的构建及筛选流程图片来源：Chin J Mod Appl Pharm,2023 March,Vol.40 No.5.DEL技术产出的临床产品DEL技术最早以科研院所为主要研究阵地，如斯坦福大学、苏黎世联邦理工学院、哈佛大学等；制药企业介入较早的为GSK，后相继有BMS、诺华、AZ，以及我国国内的成都先导、药明康德等。以GSK为例，GSK在DEL技术领域的深耕和积累相对较多，且已有多个品种进入临床。据文献报道，目前GSK正在进行包括GSK-2256294、GSK-2982772和GSK-3145095在内的多款基于DEL技术开发的药物的II期临床。其中，GSK-2256294是首个使用DEL技术鉴定的小分子药物，是一种强效、具选择性的可溶环氧化物水解酶抑制剂，临床用于治疗慢阻肺。再如GSK-2982772，是以肿瘤坏死因子介导的炎症中的RIP1激酶为靶标，通过3个氨基酸构建模块产生的77亿种化合物的文库，经亲和筛选、选择性研究、结构优化后得到了GSK-2982772，临床适应症开发为银屑病、类风湿性关节炎、溃疡性结肠炎等自免疾病。图3 利用DEL技术发现/开发的临床研究药物举例图片来源：Acta Pharmaceutica Sinica B.doi.org/10.1016/j.apsb.2024.04.006DEL国内技术布局目前，国内对于DEL技术的布局，主要以成都先导和药明康德为主，并已有业务对外服务以及产品产出。据官网介绍，成都先导聚焦小分子及核酸新药的发现与优化，着力打造了国际领先的DNA编码化合物库技术（包括DEL库的设计、合成和筛选及拓展应用）平台。目前，公司有多个内部新药项目处于临床及临床前不同阶段。官网公开了一些项目案例，如与美国辉瑞合作项目“通过DNA编码化合物库筛选发现新颖高活性NAA50抑制剂”，该项目在典型的DEL选择方案中，设置了3个样本（靶标本身，本案例为His标签的NAA50蛋白；His标签的NAA50蛋白加上饱和浓度下的抑制剂化合物1；空白对照），研究中发现NAA50蛋白在催化过程中涉及构象的变化，因此又添加了AcCoA和CoA另外两个样品，寻找与过渡态结合的化合物。最后的筛选实验设计及结果见下图。图4 成都先导-NAA50抑制剂项目部分内容图片来源：https://www.hitgen.com/cn/about-case-7.html再如，药明康德，据官网介绍DELopen平台是由药明康德联合医药研发领域顶级学术研究机构于2018年发起，致力于打造一个开放式应用和开发基因编码化合物库技术的新药研发合作平台。全球学术研究机构从事新药研发的科学家可以通过DELopen平台与工业界合作，利用最新的基因编码化合物库技术高效地完成早期药物发现。不同于成都先导的商业模式，药明康德在DEL领域更多的是提供技术服务。对此，药明康德早年间专门成立了HitS（Hit Success）事业部，整合包括DEL在内的上下游技术，以更好地赋能早期小分子新药研发客户。图5 药明康德-DELopen平台图片来源：https://www.delopen.org/未来预期大数据的背景下，随着DEL技术的发展和不断完善，必将为HIT的发现提供更好的服务支持，尤其是伴随着现有的一些问题的解决，如建库反应类型单一、库规模进一步扩大的需求、化合物的纯度保障、提升化合物的类药性等等，以及筛选、靶蛋白的选择、靶蛋白活性的控制等。另，就国内而言，目前布局的企业还不多，技术空间和服务需求相对良好，可以凭借当前的时空优势为未来的发展进行技术布局。再，新技术的开发与优化必然是企业发展所必备的条件之一，尽早的掌握、突破并形成价值，无疑将获得更多的话语权。参考1.Chin J ModAppl Pharm,2023March,Vol.40No.5.DOI:10.13748/j.cnki.issn1007-7693.202208542.Acta Pharmaceutica SinicaB.doi.org/10.1016/j.apsb.2024.04.0063.J Int Pharm Res，Vol.45，No.10，October，2018.DOI：10.13220/j.cnki.jipr.2018.10.0024.Trends in Pharmacological Sciences,January 2022,Vol.43,No.1 https://doi-org.libproxy1.nus.edu.sg/10.1016/j.tips.2021.10.0085.Acta Pharmaceutica Sinica B 2024;14(2):492e516.doi.org/10.1016/j.apsb.2023.10.0016.https://www.hitgen.com/cn/about-us.html7.https://www.wuxibiology.cn/cn/news78.《计算机做药，会比CRO更厉害吗？》，健识局封面图来源：pixabay版权声明/免责声明本文为授权转载文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢!药时代官方网站:www.drugtimes.cn联系方式:电话:13651980212微信:27674131邮箱:contact@drugtimes.cn十年之后，默沙东30亿美元重返眼科领域！错过了「星起点」宣讲会？问答实录拿走不谢～强生公布「核药」I期临床数据，4名受试者死亡！点击阅读原文，了解更多！

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