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Last update 23 Jan 2025

TrpRS

Last update 23 Jan 2025

Basic Info

Synonyms

hWRS, IFI53, IFP53

+ [10]

Introduction

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.

Drugs associated with TrpRS

M-101AI

Target

TrpRS

Mechanism

TrpRS inhibitors

Active Org.

MirimGENE Co. Ltd.Startup

Originator Org.

MirimGENE Co. Ltd.Startup

Active Indication

Sepsis

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

M-207AN

Target

TrpRS

Mechanism

TrpRS inhibitors

Active Org.

MirimGENE Co. Ltd.Startup

Originator Org.

MirimGENE Co. Ltd.Startup

Active Indication

Tuberculosis

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Chuangxinmycin

Target

TrpRS

Mechanism

TrpRS inhibitors

Active Org.

Shandong University

Originator Org.

Shandong University

Active Indication

Bacterial Infections

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with TrpRS

100 Translational Medicine associated with TrpRS

0 Patents (Medical) associated with TrpRS

427

Literatures (Medical) associated with TrpRS

01 Jan 2025·Metabolism

Wars1 downregulation in hepatocytes induces mitochondrial stress and disrupts metabolic homeostasis

Article

Author: 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.

01 Dec 2024·Cellular and Molecular Life Sciences

Tryptophanylation of insulin receptor by WARS attenuates insulin signaling

Article

Author: 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.

27 Nov 2024·Nucleic Acids Research

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

Article

Author: 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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TrpRS

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