The process of charging a cognate amino acid to tRNA, a crucial step in protein synthesis, is mediated by tRNA synthetases such as prolyl tRNA synthetase (PRS). Interestingly, unlike pan-translation inhibitors, we demonstrated that a novel small molecule PRS inhibitor (T-3861174) induced cell ...
tRNA synthetases are essential to protein synthesis. Kim and colleagues identify a non-translational function for glutamyl-prolyl-tRNA synthetase during viral infection that promotes the anti-viral activity of the antiviral signaling protein MAVS. The ma
Here, we report that anti-inflammatory AKT signaling is coordinated by glutamyl-prolyl-tRNA synthetase 1 (EPRS1). Upon inflammatory activation, AKT specifically phosphorylates Ser999 of EPRS1 in the cytoplasmic multi-tRNA synthetase complex, inducing release of EPRS1. EPRS1 compartmentalizes AKT to ...
Human EPRS1 is a 1512 amino acid-long bifunctional tRNA synthetase (Fig.1a) that resides exclusively in the MSC (Fig.1b). Due to its physical flexibility, which correlates with its multicellular functions, the overall structure of EPRS1 has not yet been determined. However, the structures of...
Translation of the glutamyl-prolyl-tRNA synthetase gene EPRS is enhanced in response to eIF2α-P. To identify the underlying mechanism of translation control, we employed biochemical approaches to determine the regulatory features by which upstream ORFs (uORFs) direct downstream translation control and...
DWN12088, an agent used for treating idiopathic pulmonary fibrosis, is a selective prolyl-tRNA synthetase (PRS) inhibitor that suppresses the synthesis of collagen. However, the mechanism underlying the hepatoprotective effect of DWN12088 is not clear. Therefore, we investigated the ro...
Objectives: This study aimed to identify novel antimalarial compounds based on allosteric inhibitor of prolyltRNA synthetase using hierarchical virtual screening. Materials and Methods: Pharmacophore model was designed initially, based on the structure-activity relationships data between sev...
The Toxoplasma gondii prolyl-tRNA synthetase inhibitor halofuginone (HFG) has been validated earlier but here we show that an ATP-mimic called L95 is a potent inhibitor and can bind to the target enzyme in the presence of HFG. Thus the two inhibitors described in this study simultaneously ...
Multiple myeloma (MM) is a plasma cell malignancy characterised by aberrant production of immunoglobulins requiring survival mechanisms to adapt to proteotoxic stress. We here show that glutamyl-prolyl-tRNA synthetase (GluProRS) inhibition constitutes a novel therapeutic target. Genomic data suggest that...
8, 9, 10, 11 EPRS is a bifunctional aminoacyl tRNA synthetase that catalyzes the aminoacylation of both glutamic acid and proline tRNA species. It is also part of the GAIT (gamma-interferon-activated inhibitor of translation) complex, which is involved in selective translational silencing of ...