Evolutionary coorigin of aminoacyl-tRNA synthetases for different amino acids, as inferred from sequence homologies

1986 ◽  
Vol 16 (3-4) ◽  
pp. 326-327 ◽  
Author(s):  
Koji Ohnishi
Keyword(s):  
Amino Acids ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
Sequence Homologies

scholarly journals Destruxin A Interacts with Aminoacyl tRNA Synthases in Bombyx mori

2021 ◽  
Vol 7 (8) ◽  
pp. 593
Author(s):  
Jingjing Wang ◽  
Alexander Berestetskiy ◽  
Qiongbo Hu
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Bombyx Mori ◽  
Metarhizium Anisopliae ◽  
Free Amino ◽  
Molecular Target ◽  
Trna Synthetases ◽  
Interaction Mode ◽  
Aminoacyl Trna Synthetases ◽  
Wide Range

Destruxin A (DA), a hexa-cyclodepsipeptidic mycotoxin produced by the entomopathogenic fungus Metarhizium anisopliae, exhibits insecticidal activities in a wide range of pests and is known as an innate immunity inhibitor. However, its mechanism of action requires further investigation. In this research, the interactions of DA with the six aminoacyl tRNA synthetases (ARSs) of Bombyx mori, BmAlaRS, BmCysRS, BmMetRS, BmValRS, BmIleRS, and BmGluProRS, were analyzed. The six ARSs were expressed and purified. The BLI (biolayer interferometry) results indicated that DA binds these ARSs with the affinity indices (KD) of 10−4 to 10−5 M. The molecular docking suggested a similar interaction mode of DA with ARSs, whereby DA settled into a pocket through hydrogen bonds with Asn, Arg, His, Lys, and Tyr of ARSs. Furthermore, DA treatments decreased the contents of soluble protein and free amino acids in Bm12 cells, which suggested that DA impedes protein synthesis. Lastly, the ARSs in Bm12 cells were all downregulated by DA stress. This study sheds light on exploring and answering the molecular target of DA against target insects.

scholarly journals Exclusive Use of trans-Editing Domains Prevents Proline Mistranslation

2013 ◽  
Vol 288 (20) ◽  
pp. 14391-14399 ◽  
Author(s):  
Oscar Vargas-Rodriguez ◽  
Karin Musier-Forsyth
Keyword(s):  
Amino Acids ◽  
Catalytic Activity ◽  
Bioinformatics Analysis ◽  
Caulobacter Crescentus ◽  
Protein A ◽  
Elongation Factor ◽  
Single Domain ◽  
Elongation Factor Tu ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases

Aminoacyl-tRNA synthetases (ARSs) catalyze the attachment of specific amino acids to cognate tRNAs. Although the accuracy of this process is critical for overall translational fidelity, similar sizes of many amino acids provide a challenge to ARSs. For example, prolyl-tRNA synthetases (ProRSs) mischarge alanine and cysteine onto tRNAPro. Many bacterial ProRSs possess an alanine-specific proofreading domain (INS) but lack the capability to edit Cys-tRNAPro. Instead, Cys-tRNAPro is cleared by a single-domain homolog of INS, the trans-editing YbaK protein. A global bioinformatics analysis revealed that there are six types of “INS-like” proteins. In addition to INS and YbaK, four additional single-domain homologs are widely distributed throughout bacteria: ProXp-ala (formerly named PrdX), ProXp-x (annotated as ProX), ProXp-y (annotated as YeaK), and ProXp-z (annotated as PA2301). The last three are domains of unknown function. Whereas many bacteria encode a ProRS containing an INS domain in addition to YbaK, many other combinations of INS-like proteins exist throughout the bacterial kingdom. Here, we focus on Caulobacter crescentus, which encodes a ProRS with a truncated INS domain that lacks catalytic activity, as well as YbaK and ProXp-ala. We show that C. crescentus ProRS can readily form Cys- and Ala-tRNAPro, and deacylation studies confirmed that these species are cleared by C. crescentus YbaK and ProXp-ala, respectively. Substrate specificity of C. crescentus ProXp-ala is determined, in part, by elements in the acceptor stem of tRNAPro and further ensured through collaboration with elongation factor Tu. These results highlight the diversity of approaches used to prevent proline mistranslation and reveal a novel triple-sieve mechanism of editing that relies exclusively on trans-editing factors.

scholarly journals The Role of Orthogonality in Genetic Code Expansion

Life ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 58 ◽  
Author(s):  
Pol Arranz-Gibert ◽  
Jaymin R. Patel ◽  
Farren J. Isaacs
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Genetic Code ◽  
Cross Reactivity ◽  
Elongation Factors ◽  
Translational Machinery ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
Genetic Code Expansion

The genetic code defines how information in the genome is translated into protein. Aside from a handful of isolated exceptions, this code is universal. Researchers have developed techniques to artificially expand the genetic code, repurposing codons and translational machinery to incorporate nonstandard amino acids (nsAAs) into proteins. A key challenge for robust genetic code expansion is orthogonality; the engineered machinery used to introduce nsAAs into proteins must co-exist with native translation and gene expression without cross-reactivity or pleiotropy. The issue of orthogonality manifests at several levels, including those of codons, ribosomes, aminoacyl-tRNA synthetases, tRNAs, and elongation factors. In this concept paper, we describe advances in genome recoding, translational engineering and associated challenges rooted in establishing orthogonality needed to expand the genetic code.

scholarly journals Quality control in tRNA charging -- editing of homocysteine.

2011 ◽  
Vol 58 (2) ◽  
Author(s):  
Hieronim Jakubowski
Keyword(s):  
Amino Acids ◽  
Quality Control ◽  
Control Point ◽  
Building Blocks ◽  
Trna Synthetase ◽  
Nutritional Deficiencies ◽  
Homocysteine Thiolactone ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
Living Organisms

All living organisms conduct protein synthesis with a high degree of accuracy maintained in the transmission and flow of information from a gene to protein product. One crucial 'quality control' point in maintaining a high level of accuracy is the selectivity by which aminoacyl-tRNA synthetases furnish correctly activated amino acids, attached to tRNA species, as the building blocks for growing protein chains. When differences in binding energies of amino acids to an aminoacyl-tRNA synthetase are inadequate, editing is used as a major determinant of enzyme selectivity. Some incorrect amino acids are edited at the active site before the transfer to tRNA (pre-transfer editing), while others are edited after transfer to tRNA at a separate editing site (post-transfer editing). Access of natural non-protein amino acids, such as homocysteine, homoserine, or ornithine to the genetic code is prevented by the editing function of aminoacyl-tRNA synthetases. Disabling editing function leads to tRNA mischarging errors and incorporation of incorrect amino acids into protein, which is detrimental to cell homeostasis and inhibits growth. Continuous homocysteine editing by methionyl-tRNA synthetase, resulting in the synthesis of homocysteine thiolactone, is part of the process of tRNA aminoacylation in living organisms, from bacteria to man. Excessive homocysteine thiolactone synthesis in hyperhomocysteinemia caused by genetic or nutritional deficiencies is linked to human vascular and neurological diseases.

scholarly journals Engineered Aminoacyl-tRNA Synthetases with Improved Selectivity toward Noncanonical Amino Acids

2019 ◽  
Vol 14 (4) ◽  
pp. 603-612 ◽  
Author(s):  
Hui Si Kwok ◽  
Oscar Vargas-Rodriguez ◽  
Sergey V. Melnikov ◽  
Dieter Söll
Keyword(s):  
Amino Acids ◽  
Noncanonical Amino Acids ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases

scholarly journals Oxidation of cellular amino acid pools leads to cytotoxic mistranslation of the genetic code

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Tammy J Bullwinkle ◽  
Noah M Reynolds ◽  
Medha Raina ◽  
Adil Moghal ◽  
Eleftheria Matsa ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Genetic Code ◽  
Trna Synthetase ◽  
Control Mechanisms ◽  
Cellular Toxicity ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
The Cost

Aminoacyl-tRNA synthetases use a variety of mechanisms to ensure fidelity of the genetic code and ultimately select the correct amino acids to be used in protein synthesis. The physiological necessity of these quality control mechanisms in different environments remains unclear, as the cost vs benefit of accurate protein synthesis is difficult to predict. We show that in Escherichia coli, a non-coded amino acid produced through oxidative damage is a significant threat to the accuracy of protein synthesis and must be cleared by phenylalanine-tRNA synthetase in order to prevent cellular toxicity caused by mis-synthesized proteins. These findings demonstrate how stress can lead to the accumulation of non-canonical amino acids that must be excluded from the proteome in order to maintain cellular viability.

Free-energy dissipation constrainst on the accuracy of enzymatic selections

1980 ◽  
Vol 13 (2) ◽  
pp. 231-254 ◽  
Author(s):  
C. Blomberg ◽  
M. Ehrenberg ◽  
C. G. Kurland
Keyword(s):  
Amino Acids ◽  
Free Energy ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
Error Frequency ◽  
Structural Differences ◽  
Cognate Trna ◽  
Selection Of

A bacterium incorporates amino acids into protein with an error frequency close to one in three thousand (Edelman & Gallant, 1977). Nevertheless, the structural differences between related amino acids are so small that it is difficult to see how they can be distinguished from each other with such accuracy (see, for example, Pauling, 1958).Indeed, the selection of amino acids during protein synthesis is carried out twice: first by the aminoacyl-tRNA synthetases and then by the codon-programmed ribosome. Each of these substrate selections is in fact a double selection. In the case of the synthetase both a particular amino acid and a corresponding cognate tRNA must be chosen to form the aminoacyl-tRNA. On the ribosome, the aminoacyl-tRNA must be matched with a cognate codon, and then the mRNA must be advanced by exactly one codon length to position the next codon in the appropriate ribosome site so that it too can be translated.

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