预约演示

更新于：2025-01-23

TrpRS

更新于：2025-01-23

基本信息

别名

hWRS、IFI53、IFP53

+ [10]

简介

Isoform 1, isoform 2 and T1-TrpRS have aminoacylation activity while T2-TrpRS lacks it. Isoform 2, T1-TrpRS and T2-TrpRS possess angiostatic activity whereas isoform 1 lacks it. T2-TrpRS inhibits fluid shear stress-activated responses of endothelial cells. Regulates ERK, Akt, and eNOS activation pathways that are associated with angiogenesis, cytoskeletal reorganization and shear stress-responsive gene expression.

关联

项与 TrpRS 相关的药物

M-101AI

靶点

TrpRS

作用机制

TrpRS inhibitors

在研机构

MirimGENE Co. Ltd.初创企业

原研机构

MirimGENE Co. Ltd.初创企业

在研适应症

脓毒症

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

M-207AN

靶点

TrpRS

作用机制

TrpRS inhibitors

在研机构

MirimGENE Co. Ltd.初创企业

原研机构

MirimGENE Co. Ltd.初创企业

在研适应症

结核

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

Chuangxinmycin

靶点

TrpRS

作用机制

TrpRS inhibitors

在研机构

山东大学

原研机构

山东大学

在研适应症

细菌感染

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 TrpRS 相关的临床结果

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100 项与 TrpRS 相关的转化医学

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0 项与 TrpRS 相关的专利（医药）

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427

项与 TrpRS 相关的文献（医药）

2025-01-01·Metabolism

Wars1 downregulation in hepatocytes induces mitochondrial stress and disrupts metabolic homeostasis

Article

作者: Benegiamo, Giorgia ; Demagny, Hadrien ; Faure, Adrien ; Auwerx, Johan ; Perino, Alessia ; Schoonjans, Kristina ; Li, Xiaoxu ; Jalil, Antoine ; Pontanari, Francesca

Several laboratories, including ours, have employed the Slc25a47^{tm1c(EUCOMM)Hmgu} mouse model to investigate the role of SLC25A47, a hepatocyte-specific mitochondrial carrier, in regulating hepatic metabolism and systemic physiology. In this study, we reveal that the hepatic and systemic phenotypes observed following recombination of the Slc25a47-Wars1 locus in hepatocytes are primarily driven by the unexpected downregulation of Wars1, the cytosolic tryptophan aminoacyl-tRNA synthetase located adjacent to Slc25a47. While the downregulation of Wars1 predictably affects cytosolic translation, we also observed a significant impairment in mitochondrial protein synthesis within hepatocytes. This disturbance in mitochondrial function leads to an activation of the mitochondrial unfolded protein response (UPR^mt), a critical component of the mitochondrial stress response (MSR). Our findings clarify the distinct roles of Slc25a47 and Wars1 in maintaining both systemic and hepatic metabolic homeostasis. This study sheds new light on the broader implications of aminoacyl-tRNA synthetases in mitochondrial physiology and stress responses.

2024-12-01·Cellular and Molecular Life Sciences

Tryptophanylation of insulin receptor by WARS attenuates insulin signaling

Article

作者: Zhao, Shi-Min ; Yuan, Yi-Yuan ; Zhang, Kai-Hui ; Hu, Song-Hua ; Zhou, Qian ; Xu, Wei ; Sun, Wen-Xing ; Lin, Yan

Increased circulating amino acid levels have been linked to insulin resistance and development of type 2 diabetes (T2D), but the underlying mechanism remains largely unknown. Herein, we show that tryptophan modifies insulin receptor (IR) to attenuate insulin signaling and impair glucose uptake. Mice fed with tryptophan-rich chow developed insulin resistance. Excessive tryptophan promoted tryptophanyl-tRNA synthetase (WARS) to tryptophanylate lysine 1209 of IR (W-K1209), which induced insulin resistance by inhibiting the insulin-stimulated phosphorylation of IR, AKT, and AS160. SIRT1, but not other sirtuins, detryptophanylated IR^W-K1209 to increase the insulin sensitivity. Collectively, we unveiled the mechanisms of how tryptophan impaired insulin signaling, and our data suggested that WARS might be a target to attenuate insulin resistance in T2D patients.

2024-11-27·Nucleic Acids Research

A genomic database furnishes minimal functional glycyl-tRNA synthetases homologous to other, designed class II urzymes

Article

作者: Patra, Sourav Kumar ; Qing, Tang Guo ; Carter, Charles W ; Douglas, Jordan ; Betts, Laurie ; Wills, Peter R

AbstractThe hypothesis that conserved core catalytic sites could represent ancestral aminoacyl-tRNA synthetases (AARS) drove the design of functional TrpRS, LeuRS, and HisRS ‘urzymes’. We describe here new urzymes detected in the genomic record of the arctic fox, Vulpes lagopus. They are homologous to the α-subunit of bacterial heterotetrameric Class II glycyl-tRNA synthetase (GlyRS-B) enzymes. AlphaFold2 predicted that the N-terminal 81 amino acids would adopt a 3D structure nearly identical to our designed HisRS urzyme (HisCA1). We expressed and purified that N-terminal segment and the spliced open reading frame GlyCA1–2. Both exhibit robust single-turnover burst sizes and ATP consumption rates higher than those previously published for HisCA urzymes and comparable to those for LeuAC and TrpAC. GlyCA is more than twice as active in glycine activation by adenosine triphosphate as the full-length GlyRS-B α2 dimer. Michaelis–Menten rate constants for all three substrates reveal significant coupling between Exon2 and both substrates. GlyCA activation favors Class II amino acids that complement those favored by HisCA and LeuAC. Structural features help explain these results. These minimalist GlyRS catalysts are thus homologous to previously described urzymes. Their properties reinforce the notion that urzymes may have the requisite catalytic activities to implement a reduced, ancestral genetic coding alphabet.

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