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Aminoacyl

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https://www.readbyqxmd.com/read/28335556/trm5-and-trmd-two-enzymes-from-distinct-origins-catalyze-the-identical-trna-modification-m%C3%A2-g37
#1
REVIEW
Sakurako Goto-Ito, Takuhiro Ito, Shigeyuki Yokoyama
The N¹-atom of guanosine at position 37 in transfer RNA (tRNA) is methylated by tRNA methyltransferase 5 (Trm5) in eukaryotes and archaea, and by tRNA methyltransferase D (TrmD) in bacteria. The resultant modified nucleotide m¹G37 positively regulates the aminoacylation of the tRNA, and simultaneously functions to prevent the +1 frameshift on the ribosome. Interestingly, Trm5 and TrmD have completely distinct origins, and therefore bear different tertiary folds. In this review, we describe the different strategies utilized by Trm5 and TrmD to recognize their substrate tRNAs, mainly based on their crystal structures complexed with substrate tRNAs...
March 21, 2017: Biomolecules
https://www.readbyqxmd.com/read/28335420/efforts-and-challenges-in-engineering-the-genetic-code
#2
REVIEW
Xiao Lin, Allen Chi Shing Yu, Ting Fung Chan
This year marks the 48th anniversary of Francis Crick's seminal work on the origin of the genetic code, in which he first proposed the "frozen accident" hypothesis to describe evolutionary selection against changes to the genetic code that cause devastating global proteome modification. However, numerous efforts have demonstrated the viability of both natural and artificial genetic code variations. Recent advances in genetic engineering allow the creation of synthetic organisms that incorporate noncanonical, or even unnatural, amino acids into the proteome...
March 14, 2017: Life
https://www.readbyqxmd.com/read/28330337/co-generating-synthetic-parts-toward-a-self-replicating-system
#3
Jun Li, Wilhelm Haas, Kirsten Jackson, Erkin Kuru, Michael C Jewett, Z Hugh Fan, Steven P Gygi, George M Church
To build replicating systems with new functions, the engineering of existing biological machineries requires a sensible strategy. Protein synthesis Using Recombinant Elements (PURE) system consists of the desired components for transcription, translation, aminoacylation and energy regeneration. PURE, might be the basis for a radically alterable, lifelike system after optimization. Here, we regenerated 54 E. coli ribosomal (r-) proteins individually from DNA templates in the PURE system. We show that using stable isotope labeling with amino acids, mass spectrometry based quantitative proteomics could detect 26 of the 33 50S and 20 of the 21 30S subunit r-proteins when co-expressed in batch format PURE system...
March 23, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28328135/confirmation-of-cagsss-syndrome-as-a-distinct-entity-in-a-danish-patient-with-a-novel-homozygous-mutation-in-iars2
#4
Shahida Moosa, Annette Haagerup, Pernille Axel Gregersen, Karin Kastberg Petersen, Janine Altmüller, Holger Thiele, Peter Nürnberg, Tae-Joon Cho, Ok-Hwa Kim, Gen Nishimura, Bernd Wollnik, Ida Vogel
Since the original description of the IARS2-related cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, skeletal dysplasia syndrome (CAGSSS; OMIM 616007) in an extended consanguineous family of French-Canadian descent, no further patients have been reported. IARS2 (OMIM 612801) encodes the mitochondrial isoleucine-tRNA synthetase which belongs to the class-I aminoacyl-tRNA synthetase family, and has been implicated in CAGSSS and a form of Leigh syndrome. Here, we report on a female Danish patient with a novel homozygous IARS2 mutation, p...
April 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28318058/nuclear-codon-reassignments-in-the-genomics-era-and-mechanisms-behind-their-evolution
#5
REVIEW
Martin Kollmar, Stefanie Mühlhausen
The canonical genetic code ubiquitously translates nucleotide into peptide sequence with several alterations known in viruses, bacteria, mitochondria, plastids, and single-celled eukaryotes. A new hypothesis to explain genetic code changes, termed tRNA loss driven codon reassignment, has been proposed recently when the polyphyly of the yeast codon reassignment events has been uncovered. According to this hypothesis, the driving force for genetic code changes are tRNA or translation termination factor loss-of-function mutations or loss-of-gene events...
March 20, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28317434/dynamics-of-the-active-site-loops-in-catalyzing-aminoacylation-reaction-in-seryl-and-histidyl-trna-synthetases
#6
Saheb Dutta, Soumya Kundu, Amrita Saha, Nilashis Nandi
Aminoacylation reaction is the first step of protein biosynthesis. The catalytic reorganization at the active site of aminoacyl tRNA synthetases (aaRSs) is driven by the loop motions. There remain lacunae of understanding concerning the catalytic loop dynamics in aaRSs. We analyzed the functional loop dynamics in seryl tRNA synthetase from Methanopyrus kandleri ((mk)SerRS) and histidyl tRNA synthetases from Thermus thermophilus ((tt)HisRS), respectively, using molecular dynamics. Results confirm that the motif 2 loop and other active site loops are flexible spots within the catalytic domain...
March 20, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28303005/ligand-co-crystallization-of-aminoacyl-trna-synthetases-from-infectious-disease-organisms
#7
Spencer O Moen, Thomas E Edwards, David M Dranow, Matthew C Clifton, Banumathi Sankaran, Wesley C Van Voorhis, Amit Sharma, Colin Manoil, Bart L Staker, Peter J Myler, Donald D Lorimer
Aminoacyl-tRNA synthetases (aaRSs) charge tRNAs with their cognate amino acid, an essential precursor step to loading of charged tRNAs onto the ribosome and addition of the amino acid to the growing polypeptide chain during protein synthesis. Because of this important biological function, aminoacyl-tRNA synthetases have been the focus of anti-infective drug development efforts and two aaRS inhibitors have been approved as drugs. Several researchers in the scientific community requested aminoacyl-tRNA synthetases to be targeted in the Seattle Structural Genomics Center for Infectious Disease (SSGCID) structure determination pipeline...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28293456/acute-digital-ischemia-a-rare-presentation-of-antisynthetase-syndrome
#8
Jin Ei Chan, Sandeep Palakodeti, Matthew J Koster
Antisynthetase syndrome (ASS) is recognized as a subgroup of idiopathic inflammatory myopathies (IIMs). It is associated with autoantibodies directed against aminoacyl-transfer ribonucleic acid (tRNA) synthetase enzymes. We report the first case of anti-PL-7/anti-SSA 52kD ASS presenting as acute digital ischemia, an association not described previously. Occlusive vasculopathy is a rare but serious manifestation that can be seen at presentation in patients with ASS and may herald the onset of severe interstitial lung disease (ILD)...
March 2017: European Journal of Rheumatology
https://www.readbyqxmd.com/read/28290293/comparative-proteomic-analysis-of-milk-derived-exosomes-in-human-and-bovine-colostrum-and-mature-milk-samples-by-itraq-coupled-lc-ms-ms
#9
Mei Yang, Dahe Song, Xueyan Cao, Rina Wu, Biao Liu, Wenhui Ye, Junrui Wu, Xiqing Yue
Exosomes are membranous vesicles found in biological fluids with important functions. However, milk-derived exosome proteins from humans and bovines have not been studied in detail. The advanced iTRAQ proteomic approach was used to analyze milk-derived exosomes in human and bovine colostrum and mature milk samples. A total of 920 milk exosome proteins were identified and quantified. Among these, 575 differentially expressed exosome proteins (P<0.05) were found. Multivariate analysis, gene ontology (GO) annotation and the KEGG pathway were used to interpret the identified proteins...
February 2017: Food Research International
https://www.readbyqxmd.com/read/28288813/a-genomically-modified-escherichia-coli-strain-carrying-an-orthogonal-e-coli-histidyl-trna-synthetase%C3%A2-trna-his-pair
#10
Markus Englert, Oscar Vargas-Rodriguez, Noah M Reynolds, Yane-Shih Wang, Dieter Söll, Takuya Umehara
BACKGROUND: Development of new aminoacyl-tRNA synthetase (aaRS)•tRNA pairs is central for incorporation of novel non-canonical amino acids (ncAAs) into proteins via genetic code expansion (GCE). The Escherichia coli and Caulobacter crescentus histidyl-tRNA synthetases (HisRS) evolved divergent mechanisms of tRNA(His) recognition that prevent their cross-reactivity. Although the E. coli HisRS•tRNA(His) pair is a good candidate for GCE, its use in C. crescentus is limited by the lack of established genetic selection methods and by the low transformation efficiency of C...
March 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28277783/origin-of-life-and-the-phosphate-transfer-catalyst
#11
Radosław W Piast, Rafał M Wieczorek
In this paper, we revisit several issues relevant to origin-of-life research and propose a Phosphate Transfer Catalyst hypothesis that furthers our understanding of some of the key events in prebiotic chemical evolution. In the Phosphate Transfer Catalyst hypothesis, we assume the existence of hypothetical metallopeptides with phosphate transfer activity that use abundant polyphosphates as both substrates and energy sources. Nonspecific catalysis by this phosphate transfer catalyst would provide a variety of different products such as phosphoryl amino acids, nucleosides, polyphosphate nucleotides, nucleic acids, and aminoacylated nucleic acids...
March 2017: Astrobiology
https://www.readbyqxmd.com/read/28271488/the-aminoacyl-trna-synthetase-complex
#12
Marc Mirande
Aminoacyl-tRNA synthetases (AARSs) are essential enzymes that specifically aminoacylate one tRNA molecule by the cognate amino acid. They are a family of twenty enzymes, one for each amino acid. By coupling an amino acid to a specific RNA triplet, the anticodon, they are responsible for interpretation of the genetic code. In addition to this translational, canonical role, several aminoacyl-tRNA synthetases also fulfill nontranslational, moonlighting functions. In mammals, nine synthetases, those specific for amino acids Arg, Asp, Gln, Glu, Ile, Leu, Lys, Met and Pro, associate into a multi-aminoacyl-tRNA synthetase complex, an association which is believed to play a key role in the cellular organization of translation, but also in the regulation of the translational and nontranslational functions of these enzymes...
2017: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/28257121/dealing%C3%A2-with%C3%A2-an%C3%A2-unconventional%C3%A2-genetic%C3%A2-code%C3%A2-in%C3%A2-mitochondria-%C3%A2-the%C3%A2-biogenesis%C3%A2-and%C3%A2-pathogenic%C3%A2-defects%C3%A2-of%C3%A2-the%C3%A2-5-formylcytosine%C3%A2-modification%C3%A2-in%C3%A2-mitochondrial%C3%A2-trna-met
#13
REVIEW
Lindsey Van Haute, Christopher A Powell, Michal Minczuk
Human mitochondria contain their own genome, which uses an unconventional genetic code. In addition to the standard AUG methionine codon, the single mitochondrial tRNA Methionine (mt-tRNAMet) also recognises AUA during translation initiation and elongation. Post-transcriptional modifications of tRNAs are important for structure, stability, correct folding and aminoacylation as well as decoding. The unique 5-formylcytosine (f5C) modification of position 34 in mt-tRNAMet has been long postulated to be crucial for decoding of unconventional methionine codons and efficient mitochondrial translation...
March 2, 2017: Biomolecules
https://www.readbyqxmd.com/read/28239189/pyrrolysyl-trna-synthetase-an-aminoacyl-trna-synthetase-for-genetic-code-expansion
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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