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https://www.readbyqxmd.com/read/28095316/rewiring-protein-synthesis-from-natural-to-synthetic-amino-acids
#1
REVIEW
Yongqiang Fan, Christopher R Evans, Jiqiang Ling
BACKGROUND: The protein synthesis machinery uses 22 natural amino acids as building blocks that faithfully decode the genetic information. Such fidelity is controlled at multiple steps and can be compromised in nature and in the laboratory to rewire protein synthesis with natural and synthetic amino acids. SCOPE OF REVIEW: This review summarizes the major quality control mechanisms during protein synthesis, including aminoacyl-tRNA synthetases, elongation factors, and the ribosome...
January 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28095181/how-trnas-dictate-nuclear-codon-reassignments-only-a-few-can-capture-non-cognate-codons
#2
Martin Kollmar, Stefanie Mühlhausen
Messenger RNA decoding by tRNAs and tRNA charging by aminoacyl-tRNA synthetases are biochemically separated processes that nevertheless in general involve the same nucleotides. The combination of charging and decoding determines the genetic code. Codon reassignment happens when a differently charged tRNA replaces a former cognate tRNA. The recent discovery of the polyphyly of the yeast CUG sense codon reassignment challenged previous mechanistic considerations and led to the proposal of the so-called tRNA loss driven codon reassignment hypothesis...
January 17, 2017: RNA Biology
https://www.readbyqxmd.com/read/28078567/the-c-abl-inhibitor-in-parkinson-disease
#3
REVIEW
Zhi-Hua Zhou, Yun-Fan Wu, Xue-Min Wang, Yong-Zhu Han
Parkinson's disease (PD) is an insidious onset neurodegenerative disease affecting approximately 1% of the population over the age of 65. So far available therapies for PD have only aimed at improving or alleviating symptoms, but not at slowing, preventing, and reversing the course of PD. Recently, some studies have indicated that the levels and activation of Abelson non-receptor tyrosine kinase (c-Abl, Abl1) were up-regulated in the brain tissue of patients with PD and demonstrated that c-Abl inhibitors could improve motor behavior, prevent the loss of dopamine neurons, inhibit phosphorylation of Cdk5, regulate α-synuclein phosphorylation and clearance, inhibit the tyrosine phosphorylation of parkin and decrease parkin substrate, for example, PARIS (zinc finger protein 746), AIMP2 (aminoacyl-tRNA synthetase-interacting multifunctional protein type2), FBP1 (fuse-binding protein 1), and synphilin-1...
January 11, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28077841/pars2-and-nars2-mutations-in-infantile-onset-neurodegenerative-disorder
#4
Takeshi Mizuguchi, Mitsuko Nakashima, Mitsuhiro Kato, Keitaro Yamada, Tohru Okanishi, Nina Ekhilevitch, Hanna Mandel, Ayelet Eran, Miyuki Toyono, Yukio Sawaishi, Hirotaka Motoi, Masaaki Shiina, Kazuhiro Ogata, Satoko Miyatake, Noriko Miyake, Hirotomo Saitsu, Naomichi Matsumoto
Here we present four unrelated families with six individuals that have infantile-onset developmental delay/regression and epilepsy. Whole-exome sequencing revealed compound heterozygous mutations, c.[283G>A];[607G>A] in a gene encoding prolyl-tRNA synthetase (PARS2) in one family. Two pairs of compound heterozygous mutations, c.[151C>T];[1184T>G] and c.[707T>G];[594+1G>A], and a homozygous mutation, c.[500A>G];[500A>G], in a gene encoding asparaginyl-tRNA synthetase (NARS2) were also identified in the other three families...
January 12, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28069943/acetylation-promotes-tyrrs-nuclear-translocation-to-prevent-oxidative-damage
#5
Xuanye Cao, Chaoqun Li, Siyu Xiao, Yunlan Tang, Jing Huang, Shuan Zhao, Xueyu Li, Jixi Li, Ruilin Zhang, Wei Yu
Tyrosyl-tRNA synthetase (TyrRS) is well known for its essential aminoacylation function in protein synthesis. Recently, TyrRS has been shown to translocate to the nucleus and protect against DNA damage due to oxidative stress. However, the mechanism of TyrRS nuclear localization has not yet been determined. Herein, we report that TyrRS becomes highly acetylated in response to oxidative stress, which promotes nuclear translocation. Moreover, p300/CBP-associated factor (PCAF), an acetyltransferase, and sirtuin 1 (SIRT1), a NAD(+)-dependent deacetylase, regulate the nuclear localization of TyrRS in an acetylation-dependent manner...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28065590/mechanism-and-evidence-of-nonsense-suppression-therapy-for-genetic-eye-disorders
#6
REVIEW
Rose Richardson, Matthew Smart, Dhani Tracey-White, Andrew Webster, Mariya Moosajee
Between 5 and 70% of genetic disease is caused by in-frame nonsense mutations, which introduce a premature termination codon (PTC) within the disease-causing gene. Consequently, during translation, non-functional or gain-of-function truncated proteins of pathological significance, are formed. Approximately 50% of all inherited retinal disorders have been associated with PTCs, highlighting the importance of novel pharmacological or gene correction therapies in ocular disease. Pharmacological nonsense suppression of PTCs could delineate a therapeutic strategy that treats the mutation in a gene- and disease-independent manner...
January 5, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28060488/aminoacyl-trna-utilizing-enzymes-in-natural-product-biosynthesis
#7
Mireille Moutiez, Pascal Belin, Muriel Gondry
Aminoacyl-tRNAs were long thought to be involved solely in ribosome-dependent protein synthesis and essential primary metabolism processes, such as targeted protein degradation and peptidoglycan synthesis. About 10 years ago, an aminoacyl-tRNA-dependent enzyme involved in the biosynthesis of the antibiotic valanimycin was discovered in a Streptomyces strain. Far from being an isolated case, this discovery has been followed by the description of an increasing number of aminoacyl-tRNA-dependent enzymes involved in secondary metabolism...
January 6, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28049726/biochemical-evidence-for-a-nuclear-modifier-allele-a10s-in-trmu-methylaminomethyl-2-thiouridylate-methyltransferase-related-to-mitochondrial-trna-modification-in-the-phenotypic-manifestation-of-deafness-associated-12s-rrna-mutation
#8
Feilong Meng, Xiaohui Cang, Yanyan Peng, Ronghua Li, Zhengyue Zhang, Fushan Li, Qingqing Fan, Anna S Guan, Nathan Fischel-Ghosian, Xiaoli Zhao, Min-Xin Guan
Nuclear modifier gene(s) was proposed to modulate the phenotypic expression of mitochondrial DNA mutation(s). Our previous investigations revealed that a nuclear modifier allele (A10S) in TRMU (methylaminomethyl-2-thiouridylate-methyltransferase) related to tRNA modification interacts with 12S rRNA 1555A>G mutation to cause deafness. The A10S mutation resided at a highly conserved residue of the N-terminal sequence. It was hypothesized that the A10S mutation altered the structure and function of TRMU, thereby causing mitochondrial dysfunction...
January 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28043061/fars2-mutation-and-epilepsy-possible-link-with-early-onset-epileptic-encephalopathy
#9
Jae So Cho, Seung Hyo Kim, Ha Young Kim, Taesu Chung, Dongsup Kim, Sesong Jang, Seung Bok Lee, Seung Keun Yoo, Jongyeon Shin, Jong-Il Kim, Hunmin Kim, Hee Hwang, Jong-Hee Chae, Jieun Choi, Ki Joong Kim, Byung Chan Lim
Early-onset epileptic encephalopathy (EOEE) consists of a heterogeneous group of epilepsy phenotypes. Recent technological advances in molecular biology have also rapidly expanded the genotype of EOEE. Genes involved in diverse molecular pathways, including ion channels, synaptic structure, transcription regulation, and cellular growth, have been implicated in EOEE. Mitochondrial aminoacyl tRNA synthetase, which plays a key role in mitochondrial protein synthesis by attaching 20 different amino acids to the tRNA tail, has been recently linked with the epilepsy phenotype...
December 2, 2016: Epilepsy Research
https://www.readbyqxmd.com/read/28039103/itraq-based-proteome-analysis-of-fluoroquinolone-resistant-staphylococcus-aureus
#10
Van Chi Thai, Teck Kwang Lim, Kim Phuong Uyen Le, Qingsong Lin, Thi Thu Hoai Nguyen
OBJECTIVES: The aim of this study was to compare global protein expression changes during fluoroquinolone (FQ) exposure of Staphylococcus aureus. METHODS: Total protein extracts of wild-type S. aureus ATCC 29213 and six multidrug-resistant (MDR) strains derived from the wild-type under different FQ exposures were analysed using the 8-plex isobaric tag for relative and absolute quantitation (iTRAQ) method combined with LC-MS/MS analysis. Differentially expressed proteins were searched for their Gene Ontology (GO) annotation (UniProt database) and protein-protein interaction network (STRING v...
December 27, 2016: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/28031151/new-derivatives-of-7-chloroquinolin-4-amine-with-antiprotozoal-activity
#11
Johanna Faist, Clemens Hinteregger, Werner Seebacher, Robert Saf, Pascal Mäser, Marcel Kaiser, Robert Weis
Novel ω-aminoacyl and -alkyl derivatives of 7-chloroquinolin-4-amine were prepared and their structures confirmed by NMR spectroscopy. Their antiprotozoal activities were examined in vitro against the sensitive NF54 strain as well as against the multiresistant K1 strain of Plasmodium falciparum and against Trypanosoma brucei rhodesiense (STIB 900). The results were compared with the activities of clinically used drugs. Their antitrypanosomal activities were only moderate whereas their antiplasmodial activities looked very promising...
December 18, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28012490/association-of-anti-aminoacyl-transfer-rna-synthetase-antibody-and-anti-melanoma-differentiation-associated-gene-5-antibody-with-the-therapeutic-response-of-polymyositis-dermatomyositis-associated-interstitial-lung-disease
#12
Naomi Yoshida, Masaki Okamoto, Shinjiro Kaieda, Kiminori Fujimoto, Tomohiro Ebata, Morihiro Tajiri, Masayuki Nakamura, Masaki Tominaga, Daisuke Wakasugi, Tomotaka Kawayama, Masataka Kuwana, Tsuneyo Mimori, Hiroaki Ida, Tomoaki Hoshino
BACKGROUND: We attempted to clarify whether the presence of anti-aminoacyl-transfer RNA synthetase antibody (anti-ARS Ab) or anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) is associated with the therapeutic response of polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD). METHODS: We retrospectively investigated 22 patients with PM/DM-ILD (10 positive for anti-ARS Ab and nine positive for anti-MDA5 Ab) for whom antibody analysis of conserved serum was possible...
January 2017: Respiratory Investigation
https://www.readbyqxmd.com/read/27992209/evaluation-of-the-hydrolysis-specificity-of-an-aminopeptidase-from-bacillus-licheniformis-swjs33-using-synthetic-peptides-and-soybean-protein-isolate
#13
Fenfen Lei, Qiangzhong Zhao, Lianzhu Lin, Baoguo Sun, Mouming Zhao
The substrate specificity of aminopeptidases has often been determined against aminoacyl-p-nitroanilide; thus, its specificity toward synthetic peptides and complex substrates remained unclear. The hydrolysis specificity of an aminopeptidase from Bacillus licheniformis SWJS33 (BLAM) was evaluated using a series of synthetic peptides and soybean protein isolate. The aminopeptidase showed high specificity for dipeptides with Leu, Val, Ala, Gly, and Phe at the N-terminus, and the specificity was significantly affected by the nature of the penultimate residue...
December 19, 2016: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/27989939/high-resolution-mass-spectrometry-based-global-proteomic-analysis-of-probiotic-strains-lactobacillus-fermentum-ncdc-400-and-rs2
#14
Parijat Pragya, Gurjeet Kaur, Syed Azmal Ali, Shveta Bhatla, Preeti Rawat, Vaibhao Lule, Sudarshan Kumar, Ashok Kumar Mohanty, Pradip Behare
Lactobacillus fermentum strains NCDC 400 and RS2, previously isolated from dairy sources, exhibited excellent probiotic properties were studied for the global proteomic profile. A total of 1125 proteins were identified by a high-resolution mass spectrometer, ESI-qTOF (nano-LC-MS/MS) in the strains of L. fermentum. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis resulted in 60.9% and 59.2% of the total proteins were functionally annotated for NCDC 400 and RS2 respectively. Simultaneously, a cluster of orthologous groups (COGs) and KEGG together revealed the presence of a significant number of proteins involved in transcription, translation, chaperones, peptidoglycan biosynthesis, nucleotide, amino acid and carbohydrate metabolism...
January 30, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/27989759/a-new-set-of-assays-for-the-discovery-of-aminoacyl-trna-synthetase-inhibitors
#15
Adélaïde Saint-Léger, Lluís Ribas de Pouplana
Current biochemical methods available to monitor the activity of aminoacyl-tRNA synthetases (ARS) are ill-suited to high-throughput screening approaches for the identification of small-molecule inhibitors of these enzymes. In an attempt to improve the limitations of current assays we have developed a suite of new methods designed to streamline the discovery of new ARS antagonists. This set of assays includes approaches to monitor ARS activity in vitro, in human cells, and in bacteria. They are applicable to several ARSs from any given organism, can be easily adapted to very high-throughput set-ups, and allow for a multi-factorial selection of drug candidates...
October 28, 2016: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/27987323/translation-system-engineering-in-escherichia-coli-enhances-non-canonical-amino-acid-incorporation-into-proteins
#16
Rui Gan, Jessica G Perez, Erik D Carlson, Ioanna Ntai, Farren J Isaacs, Neil L Kelleher, Michael C Jewett
The ability to site-specifically incorporate noncanonical amino acids (ncAAs) into proteins has made possible the study of protein structure and function in fundamentally new ways, as well as the synthesis of unnatural polymers. However, the task of site-specifically incorporating multiple ncAAs into proteins with high purity and yield continues to present a challenge. At the heart of this challenge lies the lower efficiency of engineered orthogonal translation system components compared to their natural counterparts (e...
December 17, 2016: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/27977303/tyrosyl-trna-synthetase-inhibitors-a-patent-review
#17
Juan Sun, Peng-Cheng Lv, Hai-Liang Zhu
Bacterial infection has been a consistent and relentless threat to human health because of emerging resistance to existing antibiotics. Therefore, much of the research has been focused on the design of new potent antibacterial agents. Tyrosyl-tRNA synthetase (TyrRS), as a member of aminoacyl-tRNA synthetase family, could recognize the information including the coincident tRNA molecules and the amino acids' structures, which are essential in translating the coded information into protein structures in nucleic acids...
December 15, 2016: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/27956500/inhibiting-translation-elongation-can-aid-genome-duplication-in-escherichia-coli
#18
Kamila K Myka, Michelle Hawkins, Aisha H Syeda, Milind K Gupta, Caroline Meharg, Mark S Dillingham, Nigel J Savery, Robert G Lloyd, Peter McGlynn
Conflicts between replication and transcription challenge chromosome duplication. Escherichia coli replisome movement along transcribed DNA is promoted by Rep and UvrD accessory helicases with Δrep ΔuvrD cells being inviable under rapid growth conditions. We have discovered that mutations in a tRNA gene, aspT, in an aminoacyl tRNA synthetase, AspRS, and in a translation factor needed for efficient proline-proline bond formation, EF-P, suppress Δrep ΔuvrD lethality. Thus replication-transcription conflicts can be alleviated by the partial sacrifice of a mechanism that reduces replicative barriers, namely translating ribosomes that reduce RNA polymerase backtracking...
December 11, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27940309/bacterial-aminoacyl-phospholipids-biosynthesis-and-role-in-basic-cellular-processes-and-pathogenicity
#19
REVIEW
Christoph Slavetinsky, Sebastian Kuhn, Andreas Peschel
The bacterial cell membrane accomplishes the controlled exchange of molecules with the extracellular space and mediates specific interactions with the environment. However, the cytoplasmic membrane also includes vulnerable targets for antimicrobial agents. A common feature of cationic antimicrobial peptides (CAMPs) produced by other bacteria or by the host immune system is to utilize the negative charge of bacterial phospholipids such as phosphatidylglycerol (PG) or cardiolipin (CL) for initial adherence and subsequent penetration into the membrane bilayer...
December 8, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27939931/probing-the-stereospecificity-of-tyrosyl-and-glutaminyl-trna-synthetase-with-molecular-dynamics
#20
Karen Druart, Maeva Le Guennec, Zoltan Palmai, Thomas Simonson
The stereospecificity of aminoacyl-tRNA synthetases helps exclude d-amino acids from protein synthesis and could perhaps be engineered to allow controlled d-amino acylation of tRNA. We use molecular dynamics simulations to probe the stereospecificity of the class I tyrosyl- and glutaminyl-tRNA synthetases (TyrRS, GlnRS), including wildtype enzymes and three point mutants suggested by three different protein design methods. l/d binding free energy differences are obtained by alchemically and reversibly transforming the ligand from L to D in simulations of the protein-ligand complex...
January 2017: Journal of Molecular Graphics & Modelling
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