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Information × Registration Number 0221U106051, 0114U006257 , R & D reports Title Adaptive translation and editing mechanisms of aminoacyl-tRNA synthetases in vitro and in vivo. popup.stage_title Head Tukalo Mykhailo A, Доктор біологічних наук Registration Date 04-10-2021 Organization Institute of Molecular Biology and Genetics of NAS of Ukraine popup.description2  It is shown that the editorial activity of the corrective domain of archaic leucyl-tRNA synthetase from M. thermoautotrophicus is directed against natural non-proteinogenic analogues of leucine (norvaline and norleucine). Using computational and biochemical methods, two new substrate-assisted mechanisms of hydrolysis of erroneously aminoacylated tRNA were discovered in the editing active center of prokaryotic leucyl-tRNA synthetase from Thermus thermophiles. Based on the data of molecular dynamics, the mechanism of post-transfer hydrolysis of Nva-A76 in LeuRSPh archaea is proposed, which is similar to the 2nd presented mechanism for LeuRSTt. A model for studying the erroneous incorporation of norvaline into leucine instead of E. coli proteins based on a strain with impaired leucyl-tRNA synthetase editorial activity was developed and the possibility of identifying erroneous incorporation of norvaline instead of leucine at the level of complete E. coli proteome was shown for the first time. It has been shown that the study of the in vivo incorporation of norvaline (instead of leucine) into various E. coli proteins under conditions of its increased concentration in the environment has shown to be selective and in the vast majority takes place in so-called non-vital bacteria. Using biochemical and computational methods, a new substrate-assisted mechanism of hydrolysis of D-tyrosyl-tRNATyr DTDTT has been identified, in which several functional elements of erroneously acylated tRNA are directly involved in catalysis. For the first time for aminoacyl-tRNA synthetases, it has been shown that the editing domain of alanyl-tRNA synthetase is responsible for controlling stereospecificity in the process of protein biosynthesis. The obtained results can be used for further basic research and development of inhibitors of protein biosynthesis enzymes by pathogenic microorganisms and drugs against cancer. Product Description popup.authors Gudzera Olga I. Kovalenko Oksana P. Kryklyvyi Ivan A. Rybak Mariia Yu. Yaremchuk G. D. popup.nrat_date 2021-10-04 Close