China
Africa
Explore chapters and articles related to this topic
Mitochondrial Dysfunction and Epilepsies
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Bindu Parayil Sankaran, Arun B. Taly
Mutations in genes coding mitochondrial aminoacyl-tRNA synthetases cause diseases with diverse neurological phenotypes including epileptic encephalopathies. The mitochondrial aminoacyl synthetases genes implicated in early onset epileptic encephalopathy include RARS2, FARS2, NARS2, PARS2, and VARS2. The epilepsy phenotypes are characterized by drug-resistant intractable seizures and episodes of status.
Translation and Post-Translational Modifications During Aging
Published in Alvaro Macieira-Coelho, Molecular Basis of Aging, 2017
In the case of the aaRSs, an increase or decrease in the specific activities of almost all of them has been reported in various organs of aging mice without any apparent correlation with tissue, cell type, or protein-synthetic activity. A significant decline in the specific activities of 17 aminoacyl-tRNA synthetases has been reported in the liver, lung, heart, spleen, kidney, small intestine, and skeletal muscle of aging female mice76 and during development and aging of C. elegans.77 Similarly, an increase in the proportions of the heat-labile fraction of several of these enzymes has been reported in the liver, kidney, and brain of old rats.73 However, no universal pattern can be seen for the changes in the activities of various synthetases in different organs or in different animals. Although an age-related decrease in the efficiency of aaRS can be crucial in determining the rate and accuracy of protein synthesis, direct evidence in this respect is lacking at present.
Biology of microbes
Published in Philip A. Geis, Cosmetic Microbiology, 2006
Protein synthesis is the final step in gene expression. In the following process known as translation, the mRNA nucleotide sequence is translated into the amino acid sequence of a protein. The first stage is amino acid activation by which the amino acids are attached to tRNA molecules. At one end of the tRNA molecule is a three-nucleotide anti-code that is able to match up with a complementary three-nucleotide code on the mRNA. On the other end, an attached amino acid is specific for the tRNA carrying the appropriate three-nucleotide code. An enzyme known as amino acid activating enzyme (or aminoacyl-tRNA synthetase) energizes each amino acid in order to attach it to the opposite end of the tRNA. The specificity (which amino acid goes with which tRNA) is determined by the specificity of the synthetase. Once the amino acid has been attached to one end of an adaptor, it must be linked into a chain with other amino acids in a specific order to produce a specific protein.
Utility of boron in dermatology
Published in Journal of Dermatological Treatment, 2020
David G. Jackson, Leah A. Cardwell, Elias Oussedik, Steven R. Feldman
Aminoacyl-tRNA synthetases facilitate protein synthesis by catalyzing the attachment of the proper amino acid to the tRNA. Certain aminoacyl-tRNA synthetases, such as leucyl-tRNA synthetase, have editing sites which provide proofreading capability and assurance of correct amino acid attachment. Tavaborole, a boron-based therapy for onychomycosis inhibits the fungal leucyl tRNA-synthetase thereby preventing synthesis of leucyl-tRNA and proteins (20). The boron atom in the oxaborole ring of tavaborole is vital to this mechanism of leucyl-tRNA synthetase inhibition. Tavaborole forms an adduct with leucyl-tRNA in the editing site of the leucyl tRNA synthetase enzyme, occupying the amino acid binding pocket in the editing site. The trapping of this adduct in the editing site of leucyl-tRNA synthetase facilitates inhibition of the enzyme (Figure 3).
Isolation of monoclonal antibodies from anti-synthetase syndrome patients and affinity maturation by recombination of independent somatic variants
Published in mAbs, 2020
Luke Burman, Yeeting E. Chong, Sherie Duncan, Anders Klaus, Kaitlyn Rauch, Kristina Hamel, Karine Hervé, Stephanie Pfaffen, David W. Collins, Kevin Heyries, Leslie Nangle, Carl Hansen, David J. King
Histidyl-tRNA synthetase (HARS) is one of a number of aminoacyl-tRNA synthetases that have additional functions outside of protein synthesis, with both intracellular and extracellular non-canonical functions reported.22–25 Several aminoacyl-tRNA synthetases, including HARS as well as splice variants from their genes, are secreted and have potentially important roles in regulation of the immune system.26–29 Monoclonal antibodies to HARS are, therefore, of interest for their potential ability to regulate the immune system. The rare human autoimmune disease, Jo-1 positive anti-synthetase syndrome (ASS), is characterized by the presence of autoantibodies to HARS.30 These autoantibodies remove free HARS from the circulation and are associated with individuals exhibiting activated immune pathology.29 The HARS protein can be divided into three domains: 1) an N-terminal coiled-coil WHEP domain, 2) a central catalytic domain, and 3) a C-terminal anticodon binding domain (ABD). Autoantibodies have been reported to most frequently recognize epitopes within the N- or C-terminal domains.26 In this study, we set out to isolate human monoclonal antibodies to HARS from Jo-1 positive individuals, and to investigate the generation of high-affinity antibodies using the information available in related sequences.
Advances and challenges in drug design against tuberculosis: application of in silico approaches
Published in Expert Opinion on Drug Discovery, 2019
Alexey Aleksandrov, Hannu Myllykallio
Gudzera et al. [65] proposed new inhibitors of Mtb leucyl-tRNA synthetase. Aminoacyl-tRNA synthetases catalyze attachment of amino acids to cognate tRNAs and are indispensable for protein synthesis. aatRNA synthetase structures have structural differences in prokaryotes and eukaryotes that can be exploited in the drug development. Gudzera et al. used the DOCK program to perform virtual screening of a library comprising around 100,000 molecules. The structure of Mtb LeuRS was modeled using the known Thermus thermophilus LeuRS structure as a structural template thanks to the high sequence similarity of 95% in residues comprising the active centers of these enzymes. The docking targeted the leucyl binding region in LeuRS active site. In vitro experiments revealed six compounds with inhibitory activity out 270 selected compounds. The compound with the best in vitro activity was used to retrieve additional 26 derivatives from the compound library. Three compounds out of nine tested demonstrated inhibitory activity against the Mtb H37Rv strain with a MIC of 25, 50, and 81 µM. In addition, the same authors identified the triazin-based molecules in the list of compound predicted by the in silico methods [66], which led to the discovery of compounds with IC50 of 7.6 µM and 7.2 µM against Mtb LeuRS.