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https://www.readbyqxmd.com/read/28239189/pyrrolysyl-trna-synthetase-an-aminoacyl-trna-synthetase-for-genetic-code-expansion
#1
Ana Crnković, Tateki Suzuki, Dieter Söll, Noah M Reynolds
Genetic code expansion (GCE) has become a central topic of synthetic biology. GCE relies on engineered aminoacyl-tRNA synthetases (aaRSs) and a cognate tRNA species to allow codon reassignment by co-translational insertion of non-canonical amino acids (ncAAs) into proteins. Introduction of such amino acids increases the chemical diversity of recombinant proteins endowing them with novel properties. Such proteins serve in sophisticated biochemical and biophysical studies both in vitro and in vivo, they may become unique biomaterials or therapeutic agents, and they afford metabolic dependence of genetically modified organisms for biocontainment purposes...
June 2016: Croatica Chemica Acta. Arhiv za Kemiju
https://www.readbyqxmd.com/read/28237511/coupling-genetic-code-expansion-and-metabolic-engineering-for-synthetic-cells
#2
REVIEW
Jan-Stefan Völler, Nediljko Budisa
Orthogonal protein translation with noncanonical amino acids (ncAAs) has become a standard method in biosciences. Whereas much effort is made to broaden the chemical space of ncAAs, only few attempts on their systematic low-cost in situ production are reported until now. The main aim is to engineer cells with newly designed biosynthetic pathways coupled with orthogonal aminoacyl-tRNA synthetase/tRNA pairs (o-pairs). These should provide cost-effective solutions to industrially relevant bio-production problems, such as peptide/protein production beyond the canonical set of natural molecules and to expand the arsenal of chemistries available for living cells...
February 23, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28236339/mutations-of-the-aminoacyl-trna-synthetases-sars-and-wars2-are-implicated-in-the-aetiology-of-autosomal-recessive-intellectual-disability
#3
Luciana Musante, Lucia Püttmann, Kimia Kahrizi, Masoud Garshasbi, Hao Hu, Henning Stehr, Bettina Lipkowitz, Sabine Otto, Lars R Jensen, Andreas Tzschach, Payman Jamali, Thomas Wienker, Hossein Najmabadi, Hans Hilger Ropers, Andreas W Kuss
Intellectual disability (ID) is the hallmark of an extremely heterogeneous group of disorders that comprises a wide variety of syndromic and non-syndromic phenotypes. Here we report on mutations in two aminoacyl-tRNA synthetases that are associated with ID in two unrelated Iranian families. In the first family, we identified a homozygous missense mutation (c.514G>A, p.Asp172Asn) in the cytoplasmic seryl-tRNA synthetase (SARS) gene. The mutation affects the enzymatic core domain of the protein and impairs its enzymatic activity, probably leading to reduced cytoplasmic tRNA(Ser) concentrations...
February 25, 2017: Human Mutation
https://www.readbyqxmd.com/read/28235746/exploring-the-binding-sites-of-staphylococcus-aureus-phenylalanine-trna-synthetase-a-homology-model-approach
#4
Samar S Elbaramawi, Samy M Ibrahim, El-Sayed M Lashine, Mohamed E El-Sadek, Efi Mantzourani, Claire Simons
Increased resistance of MRSA (multidrug resistance Staphylococcus aureus) to anti-infective drugs is a threat to global health necessitating the development of anti-infectives with novel mechanisms of action. Phenylalanine tRNA synthetase (PheRS) is a unique enzyme of the aminoacyl-tRNA synthetases (aaRSs), which are essential enzymes for protein biosynthesis. PheRS is an (αb)2 tetrameric enzyme composed of two alpha subunits (PheS) and two larger beta subunits (PheT). Our potential target in the drug development for the treatment of MRSA infections is the phenylalanine tRNA synthetase alpha subunit that contains the binding site for the natural substrate...
February 10, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28230768/bioinformatic-analysis-reveals-archaeal-trna-tyr-and-trna-trp-identities-in-bacteria
#5
Takahito Mukai, Noah M Reynolds, Ana Crnković, Dieter Söll
The tRNA identity elements for some amino acids are distinct between the bacterial and archaeal domains. Searching in recent genomic and metagenomic sequence data, we found some candidate phyla radiation (CPR) bacteria with archaeal tRNA identity for Tyr-tRNA and Trp-tRNA synthesis. These bacteria possess genes for tyrosyl-tRNA synthetase (TyrRS) and tryptophanyl-tRNA synthetase (TrpRS) predicted to be derived from DPANN superphylum archaea, while the cognate tRNA(Tyr) and tRNA(Trp) genes reveal bacterial or archaeal origins...
February 21, 2017: Life
https://www.readbyqxmd.com/read/28230086/classification-of-idiopathic-interstitial-pneumonias-using-anti-myxovirus-resistance-protein-1-autoantibody
#6
Yoshimasa Hamano, Hiroshi Kida, Shoichi Ihara, Akihiro Murakami, Masahiro Yanagawa, Ken Ueda, Osamu Honda, Lokesh P Tripathi, Toru Arai, Masaki Hirose, Toshimitsu Hamasaki, Yukihiro Yano, Tetsuya Kimura, Yasuhiro Kato, Hyota Takamatsu, Tomoyuki Otsuka, Toshiyuki Minami, Haruhiko Hirata, Koji Inoue, Izumi Nagatomo, Yoshito Takeda, Masahide Mori, Hiroyoshi Nishikawa, Kenji Mizuguchi, Takashi Kijima, Masanori Kitaichi, Noriyuki Tomiyama, Yoshikazu Inoue, Atsushi Kumanogoh
Chronic fibrosing idiopathic interstitial pneumonia (IIP) can be divided into two main types: idiopathic pulmonary fibrosis (IPF), a steroid-resistant and progressive disease with a median survival of 2-3 years, and idiopathic non-specific interstitial pneumonia (INSIP), a steroid-sensitive and non-progressive autoimmune disease. Although the clinical courses of these two diseases differ, they may be difficult to distinguish at diagnosis. We performed a comprehensive analysis of serum autoantibodies from patients definitively diagnosed with IPF, INSIP, autoimmune pulmonary alveolar proteinosis, and sarcoidosis...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28228619/a-case-of-anti-3-hydroxy-3-methylglutaryl-coenzyme-a-reductase-antibody-positive-paraneoplastic-necrotizing-myopathy-associated-with-advanced-gastric-cancer-that-responded-to-intravenous-immunoglobulin-therapy
#7
Tomohisa Yamaguchi, Akiko Matsunaga, Masamichi Ikawa, Norimichi Shirafuji, Ichizo Nishino, Tadanori Hamano
A 49-year-old woman presented with progressive muscle weakness of the limbs and dysphagia. Her past and family medical history were unremarkable and she did not take statins or any other medications. Laboratory tests showed that serum levels of creatine kinase were elevated (13,565 IU/l) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies were detected in the serum. Other autoantibodies to the nuclear (ANA), RNP, aminoacyl-tRNA synthetases (ARS), and signal recognition particle (SRP) were negative...
February 22, 2017: Rinshō Shinkeigaku, Clinical Neurology
https://www.readbyqxmd.com/read/28219903/myc-driven-inhibition-of-the-glutamate-cysteine-ligase-promotes-glutathione-depletion-in-liver-cancer
#8
Brittany Anderton, Roman Camarda, Sanjeev Balakrishnan, Asha Balakrishnan, Rebecca A Kohnz, Lionel Lim, Kimberley J Evason, Olga Momcilovic, Klaus Kruttwig, Qiang Huang, Guowang Xu, Daniel K Nomura, Andrei Goga
How MYC reprograms metabolism in primary tumors remains poorly understood. Using integrated gene expression and metabolite profiling, we identify six pathways that are coordinately deregulated in primary MYC-driven liver tumors: glutathione metabolism; glycine, serine, and threonine metabolism; aminoacyl-tRNA biosynthesis; cysteine and methionine metabolism; ABC transporters; and mineral absorption. We then focus our attention on glutathione (GSH) and glutathione disulfide (GSSG), as they are markedly decreased in MYC-driven tumors...
February 20, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28212794/an-efficient-system-for-incorporation-of-unnatural-amino-acids-in-response-to-the-four-base-codon-agga-in-escherichia-coli
#9
Byeong Sung Lee, Suyeon Kim, Byoung Joon Ko, Tae Hyeon Yoo
BACKGROUND: Adding new amino acids to the set of building blocks for protein synthesis expands the scope of protein engineering, and orthogonal pairs of tRNA and aminoacyl-tRNA synthetase have been developed for incorporating unnatural amino acids (UAAs) into proteins. While diverse systems have been developed to incorporate UAAs in response to the amber codon, less research has been focused on four-base codons despites their advantages. In this study, we report an efficient method to incorporate UAA in response to an AGGA codon in Escherichia coli...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28208827/on-the-uniqueness-of-the-standard-genetic-code
#10
Gabriel S Zamudio, Marco V José
In this work, we determine the biological and mathematical properties that are sufficient and necessary to uniquely determine both the primeval RNY (purine-any base-pyrimidine) code and the standard genetic code (SGC). These properties are: the evolution of the SGC from the RNY code; the degeneracy of both codes, and the non-degeneracy of the assignments of aminoacyl-tRNA synthetases (aaRSs) to amino acids; the wobbling property; the consideration that glycine was the first amino acid; the topological and symmetrical properties of both codes...
February 13, 2017: Life
https://www.readbyqxmd.com/read/28208756/homocysteine-editing-thioester-chemistry-coenzyme-a-and-the-origin-of-coded-peptide-synthesis-%C3%A2
#11
REVIEW
Hieronim Jakubowski
Aminoacyl-tRNA synthetases (AARSs) have evolved "quality control" mechanisms which prevent tRNA aminoacylation with non-protein amino acids, such as homocysteine, homoserine, and ornithine, and thus their access to the Genetic Code. Of the ten AARSs that possess editing function, five edit homocysteine: Class I MetRS, ValRS, IleRS, LeuRS, and Class II LysRS. Studies of their editing function reveal that catalytic modules of these AARSs have a thiol-binding site that confers the ability to catalyze the aminoacylation of coenzyme A, pantetheine, and other thiols...
February 9, 2017: Life
https://www.readbyqxmd.com/read/28207761/the-analysis-of-translation-related-gene-set-boosts-debates-around-origin-and-evolution-of-mimiviruses
#12
REVIEW
Jônatas Santos Abrahão, Rodrigo Araújo, Philippe Colson, Bernard La Scola
The giant mimiviruses challenged the well-established concept of viruses, blurring the roots of the tree of life, mainly due to their genetic content. Along with other nucleo-cytoplasmic large DNA viruses, they compose a new proposed order-named Megavirales-whose origin and evolution generate heated debate in the scientific community. The presence of an arsenal of genes not widespread in the virosphere related to important steps of the translational process, including transfer RNAs, aminoacyl-tRNA synthetases, and translation factors for peptide synthesis, constitutes an important element of this debate...
February 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28202229/requirement-of-the-rna-binding-protein-smpb-during-intracellular-growth-of-listeria-monocytogenes
#13
Mobarak Abu Mraheil, Renate Frantz, Lisa Teubner, Heiko Wendt, Uwe Linne, Jessica Wingerath, Thomas Wirth, Trinad Chakraborty
Bacterial trans-translation is the main quality control mechanism employed to relieve stalled ribosomes. Trans-translation is mediated by the small protein B (SmpB) and transfer-mRNA (tmRNA) ribonucleoprotein complex, which interacts with translational complexes stalled at the 3' end of non-stop mRNAs to release the stalled ribosomes thereby targeting the nascent polypeptides and truncated mRNAs for degradation. The trans-translation system exists with a few exceptions in all bacteria. In the present study, we assessed the contribution of SmpB to the growth and virulence of Listeria monocytogenes, a human intracellular food-borne pathogen that colonizes host tissues to cause severe invasive infections...
February 1, 2017: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/28192410/an-orthogonalized-platform-for-genetic-code-expansion-in-both-bacteria-and-eukaryotes
#14
James S Italia, Partha Sarathi Addy, Chester J J Wrobel, Lisa A Crawford, Marc J Lajoie, Yunan Zheng, Abhishek Chatterjee
In this study, we demonstrate the feasibility of expanding the genetic code of Escherichia coli using its own tryptophanyl-tRNA synthetase and tRNA (TrpRS-tRNA(Trp)) pair. This was made possible by first functionally replacing this endogenous pair with an E. coli-optimized counterpart from Saccharomyces cerevisiae, and then reintroducing the liberated E. coli TrpRS-tRNA(Trp) pair into the resulting strain as a nonsense suppressor, which was then followed by its directed evolution to genetically encode several new unnatural amino acids (UAAs)...
February 13, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28185908/purification-and-biophysical-characterization-of-the-aimp2-dx2-protein
#15
Roshan Jha, Hye Young Cho, Ameeq Ul Mushtaq, Kiho Lee, Dae Gyu Kim, Sunghoon Kim, Young Ho Jeon
Besides their primary role in protein synthesis, aminoacyl-tRNA synthetases (AARSs) are involved in several non-canonical processes such as apoptosis, inflammation and angiogenesis through their interactions with various cellular proteins. Nine of these AARSs interact with three aminoacyl-tRNA synthetase interacting multifunctional proteins (AIMPs), forming a multi-synthetase complex (MSC) in eukaryotes. Among the three AIMPs, AIMP2 is involved in controlling cell proliferation and apoptosis. However, a splicing variant of AIMP2 lacking exon 2, referred to as AIMP2-DX2, is oncogenic and compromises the pro-apoptotic activity of AIMP2 by competing with it for p53 and TRAF2...
February 7, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28180287/the-complex-evolutionary-history-of-aminoacyl-trna-synthetases
#16
Anargyros Chaliotis, Panayotis Vlastaridis, Dimitris Mossialos, Michael Ibba, Hubert D Becker, Constantinos Stathopoulos, Grigorios D Amoutzias
No abstract text is available yet for this article.
February 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28178239/eprs-is-a-critical-mtorc1-s6k1-effector-that-influences-adiposity-in-mice
#17
Abul Arif, Fulvia Terenzi, Alka A Potdar, Jie Jia, Jessica Sacks, Arnab China, Dalia Halawani, Kommireddy Vasu, Xiaoxia Li, J Mark Brown, Jie Chen, Sara C Kozma, George Thomas, Paul L Fox
Metabolic pathways that contribute to adiposity and ageing are activated by the mammalian target of rapamycin complex 1 (mTORC1) and p70 ribosomal protein S6 kinase 1 (S6K1) axis. However, known mTORC1-S6K1 targets do not account for observed loss-of-function phenotypes, suggesting that there are additional downstream effectors of this pathway. Here we identify glutamyl-prolyl-tRNA synthetase (EPRS) as an mTORC1-S6K1 target that contributes to adiposity and ageing. Phosphorylation of EPRS at Ser999 by mTORC1-S6K1 induces its release from the aminoacyl tRNA multisynthetase complex, which is required for execution of noncanonical functions of EPRS beyond protein synthesis...
February 16, 2017: Nature
https://www.readbyqxmd.com/read/28149956/discovery-and-investigation-of-natural-editing-function-against-artificial-amino-acids-in-protein-translation
#18
Jan-Stefan Völler, Morana Dulic, Ulla I M Gerling-Driessen, Hernan Biava, Tobias Baumann, Nediljko Budisa, Ita Gruic-Sovulj, Beate Koksch
Fluorine being not substantially present in the chemistry of living beings is an attractive element in tailoring novel chemical, biophysical, and pharmacokinetic properties of peptides and proteins. The hallmark of ribosome-mediated artificial amino acid incorporation into peptides and proteins is a broad substrate tolerance, which is assumed to rely on the absence of evolutionary pressure for efficient editing of artificial amino acids. We used the well-characterized editing proficient isoleucyl-tRNA synthetase (IleRS) from Escherichia coli to investigate the crosstalk of aminoacylation and editing activities against fluorinated amino acids...
January 25, 2017: ACS Central Science
https://www.readbyqxmd.com/read/28143889/the-structure-of-an-e-coli-trnafmet-a1-u72-variant-shows-an-unusual-conformation-of-the-a1-u72-base-pair
#19
Auriane Monestier, Alexey Aleksandrov, Pierre-Damien Coureux, Michel Panvert, Yves Mechulam, Emmanuelle Schmitt
Translation initiation in eukaryotes and archaea involves a methionylated initiator tRNA delivered to the ribosome in a ternary complex with e/aIF2 and GTP. Eukaryotic and archaeal initiator tRNAs contain a highly conserved A1-U72 base pair at the top of the acceptor stem. The importance of this base pair to discriminate initiator tRNAs from elongator tRNAs has been established previously using genetics and biochemistry. However, no structural data illustrating how the A1-U72 base pair participates in the accurate selection of the initiator tRNAs by the translation initiation systems are available...
January 31, 2017: RNA
https://www.readbyqxmd.com/read/28139725/quality-control-by-isoleucyl-trna-synthetase-of-bacillus-subtilis-is-required-for-efficient-sporulation
#20
Elizabeth Kermgard, Zhou Yang, Annika-Marisa Michel, Rachel Simari, Jacqueline Wong, Michael Ibba, Beth A Lazazzera
Isoleucyl-tRNA synthetase (IleRS) is an aminoacyl-tRNA synthetase whose essential function is to aminoacylate tRNA(Ile) with isoleucine. Like some other aminoacyl-tRNA synthetases, IleRS can mischarge tRNA(Ile) and correct this misacylation through a separate post-transfer editing function. To explore the biological significance of this editing function, we created a ileS(T233P) mutant of Bacillus subtilis that allows tRNA(Ile) mischarging while retaining wild-type Ile-tRNA(Ile) synthesis activity. As seen in other species defective for aminoacylation quality control, the growth rate of the ileS(T233P) strain was not significantly different from wild-type...
January 31, 2017: Scientific Reports
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