Article
Chemistry, Medicinal
Lianqi Sun, Shuo Zhang, Shibo Kou, Hong Yi, Along Cui, Zhuorong Li
Summary: In this study, a series of new indomycin derivatives were synthesized and evaluated for their antibacterial activity against resistant strains. The results showed that some compounds exhibited significant antibacterial activity against Staphylococcus aureus, with the isomers with natural conformations being more effective.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Young Ha Ahn, Se-Chan Oh, Shengtao Zhou, Tae-Don Kim
Summary: Tryptophanyl-tRNA synthetase (WRS) is an essential enzyme in translation and has potential pharmacological implications in diseases. Despite being primarily viewed as a Trp-producing enzyme, studies are emerging on WRS as a potential therapeutic target for drug development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Takumi Yokosawa, Keisuke Wakasugi
Summary: The study shows that Trp-deficient condition is critical for Trp uptake, not only in cells with added TrpRS protein but also in TrpRS-overexpressing cells. Tryptophanyl-AMP production by TrpRS is essential for high-affinity Trp uptake.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Tram Thuy Thuy Nguyen, Yun Hui Choi, Won-Kyu Lee, Yeounjung Ji, Eunho Chun, Yi Hyo Kim, Joo-Eun Lee, Hyun Suk Jung, Ji Hun Suh, Sunghoon Kim, Mirim Jin
Summary: While cytoplasmic tryptophanyl-tRNA synthetase (WARS1) ligates tryptophan (Trp) to its cognate tRNAs for protein synthesis, it can also be secreted through two distinct pathways: Trp-dependent secretion of naked protein and Trp-independent plasma-membrane-derived vesicles (PMVs). In the direct pathway, Trp binding induces a closed conformation of WARS1, allowing it to pass across the membrane. In the PMV-mediated secretion, WARS1 recruits activated calpain 2 and is released from PMVs, leading to inflammatory responses in vivo.
Article
Multidisciplinary Sciences
Jiaming Wang, Yue Zhang, Craig A. Mendonca, Onur Yukselen, Khaja Muneeruddin, Lingzhi Ren, Jialing Liang, Chen Zhou, Jun Xie, Jia Li, Zhong Jiang, Alper Kucukural, Scott A. Shaffer, Guangping Gao, Dan Wang
Summary: Gene therapy is a potential cure for currently untreatable diseases. This study demonstrates the successful use of recombinant adeno-associated virus (rAAV) to deliver suppressor tRNA (rAAV.sup-tRNA) and effectively treat a genetic disease in a mouse model with a nonsense mutation. The treatment lasted for more than 6 months and showed promising results for various target tissues. This research highlights the feasibility and potential benefits of using rAAV-delivered nonsense suppressor tRNAs to rescue pathogenic nonsense mutations.
Article
Chemistry, Multidisciplinary
Mariia Yu Rybak, Olga Gudzera, Oksana B. Gorbatiuk, Mariia O. Usenko, Sergiy M. Yarmoluk, Michael A. Tukalo, Galyna P. Volynets
Summary: Staphylococcus aureus is a dangerous nosocomial pathogen with multidrug resistance, making the discovery of new antibiotics essential. In this study, S. aureus threonyl-tRNA synthetase was used as a molecular target for inhibitor screening, leading to the identification of 5 active compounds out of 180 tested.
Article
Biochemistry & Molecular Biology
Elise D. Ficaretta, Chester J. J. Wrobel, Soumya J. S. Roy, Sarah B. Erickson, James S. Italia, Abhishek Chatterjee
Summary: We developed a robust and user-friendly E. coli expression system for incorporating unnatural amino acids (UAAs) into proteins. This system benefits from the use of engineered strains and vectors, allowing efficient UAA incorporation.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Rosa Merlo, Rosanna Mattossovich, Marianna Genta, Anna Valenti, Giovanni Di Mauro, Alberto Minassi, Riccardo Miggiano, Giuseppe Perugino
Summary: Self-labelling protein tags (SLPs) are versatile tools for sensor imaging that can be genetically fused with any protein of interest. Through computational and structural approaches, a thermostable CLIP-tag named SsOGT-MC8 was developed, which can covalently react with specific substrates at high temperatures.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Multidisciplinary Sciences
Noemi Gioelli, Lisa J. Neilson, Na Wei, Giulia Villari, Wenqian Chen, Bernhard Kuhle, Manuel Ehling, Federica Maione, Sander Willox, Serena Brundu, Daniele Avanzato, Grigorios Koulouras, Massimiliano Mazzone, Enrico Giraudo, Xiang-Lei Yang, Donatella Valdembri, Sara Zanivan, Guido Serini
Summary: This study reveals the role of Neuropilin1 (NRP1) and its mini-WARS ligand in reducing endothelial permeability, which plays a crucial role in the formation of a functional vascular network.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Shuai Fan, Guangxin Lv, Xiao Feng, Guangteng Wu, Yuanyuan Jin, Maocai Yan, Zhaoyong Yang
Summary: The interaction mechanism between the antimicrobial compound CXM and the bacterial enzyme TrpRS has been elucidated using X-ray crystallography and molecular dynamics simulations. This study provides insights for the screening and design of more effective CXM analogs against both Gram-negative and Gram-positive bacteria.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Qian Wang, Guiwang Zhu, Zhenming Liu
Summary: With the advancement of biophysical technology, SPR has become a crucial tool in the early drug discovery phase, offering advantages such as label-free detection and robust screening platforms. By optimizing experimental conditions, a reliable high-throughput screening system for TrpRS was successfully established, providing a scientific basis for SPR analysis of other drug targets.
ANALYTICAL BIOCHEMISTRY
(2021)
Article
Mathematics, Applied
Satoshi Tsujimoto, Luc Vinet, Alexei Zhedanov
Summary: The biorthogonal rational functions of F-3(2) type on the uniform grid demonstrate properties similar to classical orthogonal polynomials, with three different operators X, Y, Z describing these properties and generating a quadratic algebra akin to Askey-Wilson type attached to hypergeometric polynomials.
PROCEEDINGS OF THE AMERICAN MATHEMATICAL SOCIETY
(2021)
Review
Dermatology
Jiangfan Yu, Bingsi Tang, Xinglan He, Puyu Zou, Zhuotong Zeng, Rong Xiao
Summary: This article summarizes the current research status of nonsense suppression therapy for hereditary skin diseases and discusses the potential opportunities and challenges of applying new technologies related to nonsense suppression therapy to dermatology. Further research is needed to explore the potential of nonsense suppression therapy as a safer and more specific treatment strategy for hereditary skin diseases.
ACTA DERMATO-VENEREOLOGICA
(2022)
Article
Microbiology
Minoru Sasaki, Yu Shimoyama, Yoshitoyo Kodama, Taichi Ishikawa
Summary: The study revealed that WRS from THP-1 cells infected with Porphyromonas gingivalis is associated with atherosclerosis, possibly by increasing cytokine levels and upregulating the expression of leukocyte adhesion molecules and low-density lipoprotein receptors.
Article
Chemistry, Physical
Srinivas Niranj Chandrasekaran, Jhuma Das, Nikolay V. Dokholyan, Charles W. Carter
Summary: Mechanistic studies of Geobacillus stearothermophilus tryptophanyl-tRNA synthetase (TrpRS) provide a detailed description of the escapement mechanism, which efficiently converts the free energy of ATP hydrolysis into biologically useful alternative forms of information and work. Experimental and simulated melting of TrpRS reveal three transitions and ligands that stabilize the enzyme compress the temperature range over which these transitions occur. The TrpRS urzyme remains intact at the highest simulated temperatures.
STRUCTURAL DYNAMICS-US
(2023)