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tRNA Synthetase

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https://www.readbyqxmd.com/read/28809560/recombinant-macrocyclic-lanthipeptides-incorporating-non-canonical-amino-acids
#1
Claudio Zambaldo, Xiaozhou Luo, Angad P Mehta, Peter G Schultz
Nisin is a complex lanthipeptide that has broad spectrum antibacterial activity. In efforts to broaden the structural diversity of this ribosomally synthesized lantibiotic, we now report the recombinant expression of Nisin variants that incorporate noncanonical amino acids (ncAAs) at discrete positions. This is achieved by expressing the nisA structural gene, cyclase (nisC) and dehydratase (nisB), together with an orthogonal nonsense suppressor tRNA/aminoacyl-tRNA synthetase pair in Escherichia coli. A number of ncAAs with novel chemical reactivity were genetically incorporated into NisA, including an α-chloroacetamide-containing ncAA that allowed for the expression of Nisin variants with novel macrocyclic topologies...
August 15, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28808125/insights-into-substrate-promiscuity-of-human-seryl-trna-synthetase
#2
Kaitlyn M Holman, Anupama K Puppala, Jonathan W Lee, Hyun Lee, Miljan Simonovic
Seryl-tRNA synthetase (SerRS) attaches L-serine to the cognate serine tRNA (tRNA(Ser)) and the non-cognate selenocysteine tRNA (tRNA(Sec)). The latter activity initiates the anabolic cycle of selenocysteine (Sec), proper decoding of an in-frame Sec UGA codon, and synthesis of selenoproteins across all domains of life. While the accuracy of SerRS is important for overall proteome integrity, it is its substrate promiscuity that is vital for the integrity of the selenoproteome. This raises a question as to what elements in the two tRNA species, harboring different anticodon sequences and adopting distinct folds, facilitate aminoacylation by a common aminoacyl-tRNA synthetase...
August 14, 2017: RNA
https://www.readbyqxmd.com/read/28801221/the-aminoacyl-trna-synthetases-had-only-a-marginal-role-in-the-origin-of-the-organization-of-the-genetic-code-evidence-in-favor-of-the-coevolution-theory
#3
Massimo Di Giulio
The coevolution theory of the origin of the genetic code suggests that the organization of the genetic code coevolved with the biosynthetic relationships between amino acids. The mechanism that allowed this coevolution was based on tRNA-like molecules on which - this theory - would postulate the biosynthetic transformations between amino acids to have occurred. This mechanism makes a prediction on how the role conducted by the aminoacyl-tRNA synthetases (ARSs), in the origin of the genetic code, should have been...
August 9, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28797100/mapping-the-contact-surfaces-in-the-lamin-a-aimp3-complex-by-hydrogen-deuterium-exchange-ft-icr-mass-spectrometry
#4
Yeqing Tao, Pengfei Fang, Sunghoon Kim, Min Guo, Nicolas L Young, Alan G Marshall
Aminoacyl-tRNA synthetases-interacting multifunctional protein3 (AIMP3/p18) is involved in the macromolecular tRNA synthetase complex via its interaction with several aminoacyl-tRNA synthetases. Recent reports reveal a novel function of AIMP3 as a tumor suppressor by accelerating cellular senescence and causing defects in nuclear morphology. AIMP3 specifically mediates degradation of mature Lamin A (LmnA), a major component of the nuclear envelope matrix; however, the mechanism of how AIMP3 interacts with LmnA is unclear...
2017: PloS One
https://www.readbyqxmd.com/read/28777042/unexpected-metabolic-function-of-a-trna-synthetase
#5
Abul Arif, Paul L Fox
No abstract text is available yet for this article.
August 4, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28774368/-clinical-feature-and-molecular-diagnostic-analysis-of-the-first-non-caucasian-child-with-infantile-liver-failure-syndrome-type-1
#6
Wei-Xia Lin, Qi-Qi Zheng, Li Guo, Ying Cheng, Yuan-Zong Song
Infantile liver failure syndrome type 1 (ILFS1) is a Mendelian disease due to biallelic mutations in the cytoplasmic leucyl-tRNA synthetase gene (LARS). This study aimed to report the clinical and molecular features of the first non-caucasian ILFS1 patient, providing reliable evidences for the definite diagnosis of ILFS1. The 2 years and 9 months old male patient was referred to the hospital with hepatosplenomegaly over 1 year. At age 17 months, he was found to have hepatosplenomegaly and anemia. Since then, he had been managed in different hospitals...
August 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28768811/conformational-and-chemical-selection-by-a-trans-acting-editing-domain
#7
Eric M Danhart, Marina Bakhtina, William A Cantara, Alexandra B Kuzmishin, Xiao Ma, Brianne L Sanford, Marija Košutić, Yuki Goto, Hiroaki Suga, Kotaro Nakanishi, Ronald Micura, Mark P Foster, Karin Musier-Forsyth
Molecular sieves ensure proper pairing of tRNAs and amino acids during aminoacyl-tRNA biosynthesis, thereby avoiding detrimental effects of mistranslation on cell growth and viability. Mischarging errors are often corrected through the activity of specialized editing domains present in some aminoacyl-tRNA synthetases or via single-domain trans-editing proteins. ProXp-ala is a ubiquitous trans-editing enzyme that edits Ala-tRNA(Pro), the product of Ala mischarging by prolyl-tRNA synthetase, although the structural basis for discrimination between correctly charged Pro-tRNA(Pro) and mischarged Ala-tRNA(Ala) is unclear...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28758722/streptomyces-albus-a-new-cell-factory-for-non-canonical-ami-no-acids-incorporation-into-ribosomally-synthetized-natural-products
#8
Mariia Lopatniuk, Maksym Myronovskyi, Andriy Luzhetskyy
The incorporation of non-canonical amino acids (ncAAs) with different side chains into a peptide is a promising technique for changing the functional properties of that peptide. Of particular interest is the incorporation of ncAAs into peptide-derived natural products to optimize their bio-physical properties for medical and industrial applications. Here, we present the first instance of ncAAs incorporation into the natural product cinnamycin in streptomycetes using the orthogonal pyrrolysyl-tRNA synthetase/tRNAPyl pair from Methanosarcina barkeri...
July 31, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28758366/pyrrolysine-amber-stop-codon-suppression-development-and-applications
#9
Robin Brabham, Martin Anthony Fascione
The pyrrolysine tRNA synthetase-tRNA pair is likely one of the most promiscuous tRNA-synthetase pairs found in nature, capable of genetically encoding a plethora of non-canonical amino acids through stop codon reassignment. Proteins containing reactive handles, post-translational modification mimics or both can be produced in practical quantities, allowing inter alia the probing of biological pathways, the generation of antibody-drug conjugates, and enhancing protein function. This Minireview summarises the development of pyrrolysine amber stop codon suppression, presents some of the considerations required to utilise this technique to its greatest potential, and showcases the creative ways in which this technique has led to a better understanding of biological systems...
July 30, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28745975/identification-of-chemical-compounds-that-inhibit-the-function-of-histidyl-trna-synthetase-from-pseudomonas-aeruginosa
#10
Yanmei Hu, Stephanie O Palmer, Sara T Robles, Tahyra Resto, Frank B Dean, James M Bullard
Pseudomonas aeruginosa histidyl-tRNA synthetase (HisRS) was selected as a target for antibiotic drug development. The HisRS protein was overexpressed in Escherichia coli and kinetically evaluated. The KM values for interaction of HisRS with its three substrates, histidine, ATP, and tRNA(His), were 37.6, 298.5, and 1.5 μM, while the turnover numbers were 8.32, 16.8, and 0.57 s(-1), respectively. A robust screening assay was developed, and 800 natural products and 890 synthetic compounds were screened for inhibition of activity...
July 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28743072/molecular-modeling-and-molecular-dynamics-simulation-study-of-archaeal-leucyl-trna-synthetase-in-complex-with-different-mischarged-trna-in-editing-conformation
#11
A V Rayevsky, M Sharifi, M A Tukalo
Aminoacyl-tRNA synthetases (aaRSs) play important roles in maintaining the accuracy of protein synthesis. Some aaRSs accomplish this via editing mechanisms, among which leucyl-tRNA synthetase (LeuRS) edits non-cognate amino acid norvaline mainly by post-transfer editing. However, the molecular basis for this pathway for eukaryotic and archaeal LeuRS remain unclear. In this study, a complex of archaeal P. horikoshii LeuRS (PhLeuRS) with misacylated tRNA(Leu) was modeled wherever tRNA's acceptor stem was oriented directly into the editing site...
July 18, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28741290/biochemical-characterization-of-lysine-acetylation-of-tyrosyl-trna-synthetase-in-escherichia-coli
#12
Sumana Venkat, Caroline Gregory, Qinglei Gan, Chenguang Fan
Aminoacyl-tRNA synthetases (AARSs) play essential roles in protein synthesis. As a member of the AARS family, the tyrosyl-tRNA synthetase (TyrRS) in Escherichia coli has been shown to be acetylated at multiple lysine residues by proteomic studies. However, these putative acetylation targets have not been biochemically characterized yet. In this study, we applied the genetic code expansion strategy to site-specifically incorporate Nε-acetyl-L-lysine into selected positions of TyrRS for in vitro characterization...
July 24, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28737471/quality-control-by-trans-editing-factor-prevents-global-mistranslation-of-non-protein-amino-acid-%C3%AE-aminobutyrate
#13
Jo Marie Bacusmo, Alexandra B Kuzmishin, William A Cantara, Yuki Goto, Hiroaki Suga, Karin Musier-Forsyth
Accuracy in protein biosynthesis is maintained through multiple pathways, with a critical checkpoint occurring at the tRNA aminoacylation step catalyzed by aminoacyl-tRNA synthetases (ARSs). In addition to the editing functions inherent to some synthetases, single-domain trans-editing factors, which are structurally homologous to ARS editing domains, have evolved as alternative mechanisms to correct mistakes in aminoacyl-tRNA synthesis. To date, ARS-like trans-editing domains have been shown to act on specific tRNAs that are mischarged with genetically encoded amino acids...
July 24, 2017: RNA Biology
https://www.readbyqxmd.com/read/28732448/synthesis-of-a-bicyclic-azetidine-with-in-vivo-antimalarial-activity-enabled-by-stereospecific-directed-c-sp-3-h-arylation
#14
Micah Maetani, Jochen Zoller, Bruno Melillo, Oscar Verho, Nobutaka Kato, Jun Pu, Eamon Comer, Stuart L Schreiber
The development of new antimalarial therapeutics is necessary to address the increasing resistance to current drugs. Bicyclic azetidines targeting Plasmodium falciparum phenylalanyl-tRNA synthetase comprise one promising new class of antimalarials, especially due to their activities against three stages of the parasite's life cycle, but a lengthy synthetic route to these compounds may affect the feasibility of delivering new therapeutic agents within the cost constraints of antimalarial drugs. Here, we report an efficient synthesis of antimalarial compound BRD3914 (EC50 = 15 nM) that hinges on a Pd-catalyzed, directed C(sp(3))-H arylation of azetidines at the C3 position...
August 16, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28723566/genome-wide-rnai-screen-for-fat-regulatory-genes-in-c-%C3%A2-elegans-identifies-a-proteostasis-ampk-axis-critical-for-starvation-survival
#15
Christopher M Webster, Elizabeth C Pino, Christopher E Carr, Lianfeng Wu, Ben Zhou, Lucydalila Cedillo, Michael C Kacergis, Sean P Curran, Alexander A Soukas
Organisms must execute metabolic defenses to survive nutrient deprivation. We performed a genome-wide RNAi screen in Caenorhabditis elegans to identify fat regulatory genes indispensable for starvation resistance. Here, we show that opposing proteostasis pathways are principal determinants of starvation survival. Reduced function of cytoplasmic aminoacyl tRNA synthetases (ARS genes) increases fat mass and extends starvation survival, whereas reduced proteasomal function reduces fat and starvation survival. These opposing pathways converge on AMP-activated protein kinase (AMPK) as the critical effector of starvation defenses...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28720827/small-chaperons-and-autophagy-protected-neurons-from-necrotic-cell-death
#16
Ye Lei, Kai Liu, Lin Hou, Lianggong Ding, Yuhong Li, Lei Liu
Neuronal necrosis occurs during early phase of ischemic insult. However, our knowledge of neuronal necrosis is still inadequate. To study the mechanism of neuronal necrosis, we previously established a Drosophila genetic model of neuronal necrosis by calcium overloading through expression of a constitutively opened cation channel mutant. Here, we performed further genetic screens and identified a suppressor of neuronal necrosis, CG17259, which encodes a seryl-tRNA synthetase. We found that loss-of-function (LOF) CG17259 activated eIF2α phosphorylation and subsequent up-regulation of chaperons (Hsp26 and Hsp27) and autophagy...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720599/hyperacute-muscle-weakness-in-an-unusual-coexistence-of-antisignal-recognition-particle-and-anti-mi-2-antibodies
#17
Richard Oluyinka Akintayo, Olanrewaju Festus Agbola, Abiodun Waliyullah Adeyemo, Olufemi Adelowo
Idiopathic inflammatory myopathies are a heterogeneous group of systemic diseases characterised by variable phenotypes of chronic progressive muscle weakness. Myositis-specific antibodies (MSAs) include antibodies to cytoplasmic signal recognition particle (SRP) and various tRNA synthetases as well as the nuclear helicase protein Mi-2. These antibodies are typically found only in a fraction of true myositis cases and they tend to be mutually exclusive. Few cases of coexistence of two MSAs in the same patient have been reported and these cases all involve an antisynthetase antibody coexisting with either anti-SRP or anti-Mi-2 antibody...
July 18, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28716624/recent-advances-in-mitochondrial-aminoacyl-trna-synthetases-and-disease
#18
REVIEW
Marie Sissler, Ligia Elena González-Serrano, Eric Westhof
Dysfunctions in mitochondria - the powerhouses of the cell - lead to several human pathologies. Because mitochondria integrate nuclear and mitochondrial genetic systems, they are richly intertwined with cellular activities. The nucleus-encoded mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) are key components of the mitochondrial translation apparatus. Mutations in these enzymes predominantly affect the central nervous system (CNS) but also target other organs. Comparable mutations in mt-aaRSs can lead to vastly diverse diseases, occurring at different stages in life, and within different tissues; this represents a confounding issue...
July 14, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28716262/new-genetic-causes-for-complex-hereditary-spastic-paraplegia
#19
Paulo Victor Sgobbi de Souza, Thiago Bortholin, Renan Braido Dias, Marco Antônio Troccoli Chieia, Stênio Burlin, Fernando George Monteiro Naylor, Wladimir Bocca Vieira de Rezende Pinto, Acary Souza Bulle Oliveira
INTRODUCTION: Hereditary Spastic Paraplegia (HSP) represents a complex and heterogeneous group of rare neurodegenerative disorders that share a common clinical feature of weakness and lower limb spasticity that can occur alone or in combination with a constellation of other neurological or systemic signs and symptoms. Although the core clinical feature of weakness and lower limb spasticity is virtually universal, the genetic heterogeneity is almost uncountable with more than 70 genetic forms described so far...
August 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28679377/methionyl-trna-synthetase-overexpression-is-associated-with-poor-clinical-outcomes-in-non-small-cell-lung-cancer
#20
Eun Young Kim, Ji Ye Jung, Arum Kim, Kwangsoo Kim, Yoon Soo Chang
BACKGROUND: Methionyl-tRNA synthetase (MRS) plays a critical role in initiating translation by transferring Met to the initiator tRNA (tRNAi(Met)) and protection against ROS-mediated damage, suggesting that its overexpression is related to cancer growth and drug resistance. In this study, the clinical implication of MRS expression in non-small cell lung cancer (NSCLC) was evaluated. METHODS: Immunoblot and immunohistochemical (IHC) analyses were performed using tissue lysates and formalin-fixed paraffin embedded (FFPE) tissue blocks from wild type C57BL/6, LSL-Kras G12D, and LSL-Kras G12D:p53(fl/fl) mice...
July 5, 2017: BMC Cancer
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