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Pesquisa : D08.811.464.263.200.800 [Categoria DeCS]
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[PMID]:27542414
[Au] Autor:Zhou XL; Chen Y; Fang ZP; Ruan ZR; Wang Y; Liu RJ; Xue MQ; Wang ED
[Ad] Endereço:From the State Key Laboratory of Molecular Biology, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200031 Shanghai, China and.
[Ti] Título:Translational Quality Control by Bacterial Threonyl-tRNA Synthetases.
[So] Source:J Biol Chem;291(40):21208-21221, 2016 Sep 30.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Translational fidelity mediated by aminoacyl-tRNA synthetases ensures the generation of the correct aminoacyl-tRNAs, which is critical for most species. Threonyl-tRNA synthetase (ThrRS) contains multiple domains, including an N2 editing domain. Of the ThrRS domains, N1 is the last to be assigned a function. Here, we found that ThrRSs from Mycoplasma species exhibit differences in their domain composition and editing active sites compared with the canonical ThrRSs. The Mycoplasma mobile ThrRS, the first example of a ThrRS naturally lacking the N1 domain, displays efficient post-transfer editing activity. In contrast, the Mycoplasma capricolum ThrRS, which harbors an N1 domain and a degenerate N2 domain, is editing-defective. Only editing-capable ThrRSs were able to support the growth of a yeast thrS deletion strain (ScΔthrS), thus suggesting that ScΔthrS is an excellent tool for studying the in vivo editing of introduced bacterial ThrRSs. On the basis of the presence or absence of an N1 domain, we further revealed the crucial importance of the only absolutely conserved residue within the N1 domain in regulating editing by mediating an N1-N2 domain interaction in Escherichia coli ThrRS. Our results reveal the translational quality control of various ThrRSs and the role of the N1 domain in translational fidelity.
[Mh] Termos MeSH primário: Proteínas de Bactérias
Mycoplasma capricolum
Biossíntese de Proteínas/fisiologia
Treonina-tRNA Ligase
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Escherichia coli/genética
Escherichia coli/metabolismo
Deleção de Genes
Teste de Complementação Genética
Mycoplasma capricolum/enzimologia
Mycoplasma capricolum/genética
Domínios Proteicos
Saccharomyces cerevisiae/genética
Saccharomyces cerevisiae/metabolismo
Especificidade da Espécie
Treonina-tRNA Ligase/genética
Treonina-tRNA Ligase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); EC 6.1.1.3 (Threonine-tRNA Ligase)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170930
[Lr] Data última revisão:
170930
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160821
[St] Status:MEDLINE


  2 / 191 MEDLINE  
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[PMID]:27447614
[Au] Autor:Li M; Wen F; Zhao S; Wang P; Li S; Zhang Y; Zheng N; Wang J
[Ad] Endereço:Ministry of Agriculture Laboratory of Quality & Safety Risk Assessment for Dairy Products (Beijing), Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. liming01@caas.cn.
[Ti] Título:Exploring the Molecular Basis for Binding of Inhibitors by Threonyl-tRNA Synthetase from Brucella abortus: A Virtual Screening Study.
[So] Source:Int J Mol Sci;17(7), 2016 Jul 19.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Targeting threonyl-tRNA synthetase (ThrRS) of Brucella abortus is a promising approach to developing small-molecule drugs against bovine brucellosis. Using the BLASTp algorithm, we identified ThrRS from Escherichia coli (EThrRS, PDB ID 1QF6), which is 51% identical to ThrRS from Brucella abortus (BaThrRS) at the amino acid sequence level. EThrRS was used as the template to construct a BaThrRS homology model which was optimized using molecular dynamics simulations. To determine the residues important for substrate ATP binding, we identified the ATP-binding regions of BaThrRS, docked ATP to the protein, and identified the residues whose side chains surrounded bound ATP. We then used the binding site of ATP to virtually screen for BaThrRS inhibitors and got seven leads. We further characterized the BaThrRS-binding site of the compound with the highest predicted inhibitory activity. Our results should facilitate future experimental effects to find novel drugs for use against bovine brucellosis.
[Mh] Termos MeSH primário: Trifosfato de Adenosina/metabolismo
Antibacterianos/metabolismo
Brucella abortus/enzimologia
Inibidores Enzimáticos/metabolismo
Treonina-tRNA Ligase/antagonistas & inibidores
Treonina-tRNA Ligase/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Sítios de Ligação
Brucelose Bovina/tratamento farmacológico
Brucelose Bovina/microbiologia
Bovinos
Modelos Moleculares
Simulação de Dinâmica Molecular
Homologia de Sequência de Aminoácidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Enzyme Inhibitors); 8L70Q75FXE (Adenosine Triphosphate); EC 6.1.1.3 (Threonine-tRNA Ligase)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170411
[Lr] Data última revisão:
170411
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160723
[St] Status:MEDLINE


  3 / 191 MEDLINE  
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[PMID]:27214289
[Au] Autor:Deakin CT; Yasin SA; Simou S; Arnold KA; Tansley SL; Betteridge ZE; McHugh NJ; Varsani H; Holton JL; Jacques TS; Pilkington CA; Nistala K; Wedderburn LR; UK Juvenile Dermatomyositis Research Group
[Ad] Endereço:University College London, London, UK.
[Ti] Título:Muscle Biopsy Findings in Combination With Myositis-Specific Autoantibodies Aid Prediction of Outcomes in Juvenile Dermatomyositis.
[So] Source:Arthritis Rheumatol;68(11):2806-2816, 2016 Nov.
[Is] ISSN:2326-5205
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Juvenile dermatomyositis (DM) is a rare and severe autoimmune condition characterized by rash and proximal muscle weakness. While some patients respond to standard treatment, others do not. This study was carried out to investigate whether histopathologic findings and myositis-specific autoantibodies (MSAs) have prognostic significance in juvenile DM. METHODS: Muscle biopsy samples (n = 101) from patients in the UK Juvenile Dermatomyositis Cohort and Biomarker Study were stained, analyzed, and scored for severity of histopathologic features. In addition, autoantibodies were measured in the serum or plasma of patients (n = 90) and longitudinal clinical data were collected (median duration of follow-up 4.9 years). Long-term treatment status (on or off medication over time) was modeled using generalized estimating equations. RESULTS: Muscle biopsy scores differed according to MSA subgroup. When the effects of MSA subgroup were accounted for, increased severity of muscle histopathologic features was predictive of an increased risk of remaining on treatment over time: for the global pathology score (histopathologist's visual analog scale [hVAS] score), 1.48-fold higher odds (95% confidence interval [95% CI] 1.12-1.96; P = 0.0058), and for the total biopsy score (determined with the standardized score tool), 1.10-fold higher odds (95% CI 1.01-1.21; P = 0.038). A protective effect was identified in patients with anti-Mi-2 autoantibodies, in whom the odds of remaining on treatment were 7.06-fold lower (95% CI 1.41-35.36; P = 0.018) despite muscle biopsy scores indicating more severe disease. In patients with anti-nuclear matrix protein 2 autoantibodies, anti-transcription intermediary factor 1γ autoantibodies, or no detectable autoantibody, increased histopathologic severity alone, without adjustment for the effect of MSA subtype, was predictive of the risk of remaining on treatment: for the hVAS global pathology score, 1.61-fold higher odds (95% CI 1.16-2.22; P = 0.004), and for the total biopsy score, 1.13-fold higher odds (95% CI 1.03-1.24; P = 0.013). CONCLUSION: Histopathologic severity, in combination with MSA subtype, is predictive of the risk of remaining on treatment in patients with juvenile DM and may be useful for discussing probable treatment length with parents and patients. Understanding these associations may identify patients at greater risk of severe disease.
[Mh] Termos MeSH primário: Autoanticorpos/imunologia
Dermatomiosite/patologia
Músculo Quadríceps/patologia
[Mh] Termos MeSH secundário: Corticosteroides/uso terapêutico
Criança
Pré-Escolar
Estudos de Coortes
DNA Topoisomerases/imunologia
Proteínas de Ligação a DNA/imunologia
Dermatomiosite/tratamento farmacológico
Dermatomiosite/imunologia
Feminino
Seres Humanos
Imunossupressores/uso terapêutico
Helicase IFIH1 Induzida por Interferon/imunologia
Estudos Longitudinais
Masculino
Metotrexato/uso terapêutico
Razão de Chances
Prognóstico
Fatores de Proteção
Fatores de Risco
Índice de Gravidade de Doença
Partícula de Reconhecimento de Sinal/imunologia
Treonina-tRNA Ligase/imunologia
Fatores de Transcrição/imunologia
Reino Unido
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrenal Cortex Hormones); 0 (Autoantibodies); 0 (DNA-Binding Proteins); 0 (Immunosuppressive Agents); 0 (Mi-2 antibodies); 0 (Signal Recognition Particle); 0 (TRIM33 protein, human); 0 (Transcription Factors); 0 (nuclear matrix protein 2); EC 3.6.1.- (IFIH1 protein, human); EC 3.6.4.13 (Interferon-Induced Helicase, IFIH1); EC 5.99.1.- (DNA Topoisomerases); EC 6.1.1.3 (Threonine-tRNA Ligase); YL5FZ2Y5U1 (Methotrexate)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:160524
[St] Status:MEDLINE
[do] DOI:10.1002/art.39753


  4 / 191 MEDLINE  
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[PMID]:27010025
[Au] Autor:Lounsbury KM; Francklyn CS
[Ad] Endereço:From the Departments of Pharmacology (K.M.L.) and Biochemistry (C.S.F.), University of Vermont, College of Medicine, Burlington. karen.lounsbury@uvm.edu.
[Ti] Título:Aminoacyl-Transfer RNA Synthetases: Connecting Nutrient Status to Angiogenesis Through the Unfolded Protein Response.
[So] Source:Arterioscler Thromb Vasc Biol;36(4):582-3, 2016 Apr.
[Is] ISSN:1524-4636
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Isoleucina-tRNA Ligase/deficiência
Neovascularização Fisiológica
Treonina-tRNA Ligase/deficiência
Resposta a Proteínas não Dobradas
Proteínas de Peixe-Zebra/deficiência
[Mh] Termos MeSH secundário: Animais
[Pt] Tipo de publicação:COMMENT; EDITORIAL; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Zebrafish Proteins); EC 6.1.1.3 (Threonine-tRNA Ligase); EC 6.1.1.5 (Isoleucine-tRNA Ligase)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:170403
[Lr] Data última revisão:
170403
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160325
[St] Status:MEDLINE
[do] DOI:10.1161/ATVBAHA.116.307193


  5 / 191 MEDLINE  
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[PMID]:26993167
[Au] Autor:Cao Z; Wang H; Mao X; Luo L
[Ad] Endereço:Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Beibei, 400715, Chongqing, China.
[Ti] Título:Noncanonical function of threonyl-tRNA synthetase regulates vascular development in zebrafish.
[So] Source:Biochem Biophys Res Commun;473(1):67-72, 2016 Apr 22.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The canonical functions of Aminoacyl-tRNA synthetases (AARSs) are indispensable for protein synthesis. However, recent evidence indicates that some AARSs possess additional biological functions (noncanonical functions) related to immune responses and vascular development. Here, we identified a zebrafish cq16 mutant presenting the disorganized vessels with abnormal branching of the established intersegmental vessels (ISVs) as well as aberrant patterning of the brain vascular network after 50 h post fertilization. The cq16 mutant gene is responsible for encoding threonyl-tRNA synthetase (tars) with a missense mutation. The abnormal branching of ISVs was caused by the increased expression of vascular endothelial growth factor A (vegfa) in tars(cq16) mutant. Inhibition of Vegf signaling suppresses the abnormal vascular branching observed in tars(cq16) mutant. Furthermore, injection of human TARS mRNA potently reduced the vascular aberrant branching in tars(cq16) mutant, indicating a conserved function of tars in regulating angiogenesis between zebrafish and human. Therefore, we conclude that noncanonical function of tars regulates vascular development presumably by modulating the expression of vegfa.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica no Desenvolvimento
Neovascularização Fisiológica
Treonina-tRNA Ligase/genética
Treonina-tRNA Ligase/fisiologia
Proteínas de Peixe-Zebra/fisiologia
Peixe-Zebra/fisiologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Vasos Sanguíneos/fisiologia
Sistemas CRISPR-Cas
Circulação Cerebrovascular/fisiologia
Mapeamento Cromossômico
Sequência Conservada
Genótipo
Células Endoteliais da Veia Umbilical Humana
Seres Humanos
Hibridização In Situ
Dados de Sequência Molecular
Morfogênese
Mutação
Mutação de Sentido Incorreto
RNA Mensageiro/metabolismo
Homologia de Sequência de Aminoácidos
Transdução de Sinais
Fator A de Crescimento do Endotélio Vascular/fisiologia
Proteínas de Peixe-Zebra/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (RNA, Messenger); 0 (VEGF protein, zebrafish); 0 (Vascular Endothelial Growth Factor A); 0 (Zebrafish Proteins); EC 6.1.1.3 (Threonine-tRNA Ligase)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:170802
[Lr] Data última revisão:
170802
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160320
[St] Status:MEDLINE


  6 / 191 MEDLINE  
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[PMID]:26821951
[Au] Autor:Castranova D; Davis AE; Lo BD; Miller MF; Paukstelis PJ; Swift MR; Pham VN; Torres-Vázquez J; Bell K; Shaw KM; Kamei M; Weinstein BM
[Ad] Endereço:From the Program in Genomics of Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD (D.C., A.E.D., B.D.L., M.F.M., M.R.S., V.N.P., J.T.-V., K.B., K.M.S., M.K., B.M.W.); and Department of Chemistry and Biochemistry, College of Compute
[Ti] Título:Aminoacyl-Transfer RNA Synthetase Deficiency Promotes Angiogenesis via the Unfolded Protein Response Pathway.
[So] Source:Arterioscler Thromb Vasc Biol;36(4):655-62, 2016 Apr.
[Is] ISSN:1524-4636
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Understanding the mechanisms regulating normal and pathological angiogenesis is of great scientific and clinical interest. In this report, we show that mutations in 2 different aminoacyl-transfer RNA synthetases, threonyl tRNA synthetase (tars(y58)) or isoleucyl tRNA synthetase (iars(y68)), lead to similar increased branching angiogenesis in developing zebrafish. APPROACH AND RESULTS: The unfolded protein response pathway is activated by aminoacyl-transfer RNA synthetase deficiencies, and we show that unfolded protein response genes atf4, atf6, and xbp1, as well as the key proangiogenic ligand vascular endothelial growth factor (vegfaa), are all upregulated in tars(y58) and iars(y68) mutants. Finally, we show that the protein kinase RNA-like endoplasmic reticulum kinase-activating transcription factor 4 arm of the unfolded protein response pathway is necessary for both the elevated vegfaa levels and increased angiogenesis observed in tars(y58) mutants. CONCLUSIONS: Our results suggest that endoplasmic reticulum stress acts as a proangiogenic signal via unfolded protein response pathway-dependent upregulation of vegfaa.
[Mh] Termos MeSH primário: Isoleucina-tRNA Ligase/deficiência
Neovascularização Fisiológica
Treonina-tRNA Ligase/deficiência
Resposta a Proteínas não Dobradas
Proteínas de Peixe-Zebra/deficiência
[Mh] Termos MeSH secundário: Fator 4 Ativador da Transcrição/genética
Fator 4 Ativador da Transcrição/metabolismo
Fator 6 Ativador da Transcrição/genética
Fator 6 Ativador da Transcrição/metabolismo
Animais
Animais Geneticamente Modificados
Proteínas de Ligação a DNA/genética
Proteínas de Ligação a DNA/metabolismo
Retículo Endoplasmático/metabolismo
Estresse do Retículo Endoplasmático
Regulação da Expressão Gênica no Desenvolvimento
Genótipo
Isoleucina-tRNA Ligase/genética
Mutação
Fenótipo
Fatores de Transcrição de Fator Regulador X
Transdução de Sinais
Treonina-tRNA Ligase/genética
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
Fator A de Crescimento do Endotélio Vascular/genética
Fator A de Crescimento do Endotélio Vascular/metabolismo
Proteína 1 de Ligação a X-Box
Peixe-Zebra
Proteínas de Peixe-Zebra/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., INTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; VIDEO-AUDIO MEDIA
[Nm] Nome de substância:
0 (Activating Transcription Factor 6); 0 (DNA-Binding Proteins); 0 (Regulatory Factor X Transcription Factors); 0 (Transcription Factors); 0 (Vascular Endothelial Growth Factor A); 0 (X-Box Binding Protein 1); 0 (XBP1 protein, human); 0 (Zebrafish Proteins); 145891-90-3 (Activating Transcription Factor 4); EC 6.1.1.3 (Threonine-tRNA Ligase); EC 6.1.1.5 (Isoleucine-tRNA Ligase)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:170403
[Lr] Data última revisão:
170403
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160130
[St] Status:MEDLINE
[do] DOI:10.1161/ATVBAHA.115.307087


  7 / 191 MEDLINE  
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[PMID]:26811336
[Au] Autor:Wang Y; Zhou XL; Ruan ZR; Liu RJ; Eriani G; Wang ED
[Ad] Endereço:From the State Key Laboratory of Molecular Biology, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China, the School of L
[Ti] Título:A Human Disease-causing Point Mutation in Mitochondrial Threonyl-tRNA Synthetase Induces Both Structural and Functional Defects.
[So] Source:J Biol Chem;291(12):6507-20, 2016 Mar 18.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mitochondria require all translational components, including aminoacyl-tRNA synthetases (aaRSs), to complete organelle protein synthesis. Some aaRS mutations cause mitochondrial disorders, including human mitochondrial threonyl-tRNA synthetase (hmtThrRS) (encoded by TARS2), the P282L mutation of which causes mitochondrial encephalomyopathies. However, its catalytic and structural consequences remain unclear. Herein, we cloned TARS2 and purified the wild-type and P282L mutant hmtThrRS. hmtThrRS misactivates non-cognate Ser and uses post-transfer editing to clear erroneously synthesized products. In vitro and in vivo analyses revealed that the mutation induces a decrease in Thr activation, aminoacylation, and proofreading activities and a change in the protein structure and/or stability, which might cause reduced catalytic efficiency. We also identified a splicing variant of TARS2 mRNA lacking exons 8 and 9, the protein product of which is targeted into mitochondria. In HEK293T cells, the variant does not dimerize and cannot complement the ThrRS knock-out strain in yeast, suggesting that the truncated protein is inactive and might have a non-canonical function, as observed for other aaRS fragments. The present study describes the aminoacylation and editing properties of hmtThrRS, clarifies the molecular consequences of the P282L mutation, and shows that the yeast ThrRS-deletion model is suitable to test pathology-associated point mutations or alternative splicing variants of mammalian aaRS mRNAs.
[Mh] Termos MeSH primário: Encefalomiopatias Mitocondriais/genética
Treonina-tRNA Ligase/genética
[Mh] Termos MeSH secundário: Monofosfato de Adenosina/química
Processamento Alternativo
Sequência de Aminoácidos
Ativação Enzimática
Estabilidade Enzimática
Teste de Complementação Genética
Células HEK293
Seres Humanos
Isoenzimas/química
Isoenzimas/genética
Isoenzimas/metabolismo
Cinética
Mitocôndrias/enzimologia
Modelos Moleculares
Dados de Sequência Molecular
Mutação Puntual
Multimerização Proteica
Transporte Proteico
Saccharomyces cerevisiae/genética
Serina/química
Treonina/química
Treonina-tRNA Ligase/química
Treonina-tRNA Ligase/metabolismo
Aminoacilação de RNA de Transferência
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Isoenzymes); 2ZD004190S (Threonine); 415SHH325A (Adenosine Monophosphate); 452VLY9402 (Serine); EC 6.1.1.3 (Threonine-tRNA Ligase)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:170318
[Lr] Data última revisão:
170318
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160127
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M115.700849


  8 / 191 MEDLINE  
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[PMID]:26704982
[Au] Autor:Holman KM; Wu J; Ling J; Simonovic M
[Ad] Endereço:Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA.
[Ti] Título:The crystal structure of yeast mitochondrial ThrRS in complex with the canonical threonine tRNA.
[So] Source:Nucleic Acids Res;44(3):1428-39, 2016 Feb 18.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In mitochondria of Saccharomyces cerevisiae, a single aminoacyl-tRNA synthetase (aaRS), MST1, aminoacylates two isoacceptor tRNAs, tRNA1(Thr) and tRNA2(Thr), that harbor anticodon loops of different size and sequence. As a result of this promiscuity, reassignment of the CUN codon box from leucine to threonine is facilitated. However, the mechanism by which a single aaRS binds distinct anticodon loops with high specificity is not well understood. Herein, we present the crystal structure of MST1 in complex with the canonical tRNA2(Thr) and non-hydrolyzable analog of threonyl adenylate. Our structure reveals that the dimeric arrangement of MST1 is essential for binding the 5'-phosphate, the second base pair of the acceptor stem, the first two base pairs of the anticodon stem and the first nucleotide of the variable arm. Further, in contrast to the bacterial ortholog that 'reads' the entire anticodon sequence, MST1 recognizes bases in the second and third position and the nucleotide upstream of the anticodon sequence. We speculate that a flexible loop linking strands ß4 and ß5 may be allosteric regulator that establishes cross-subunit communication between the aminoacylation and tRNA-binding sites. We also propose that structural features of the anticodon-binding domain in MST1 permit binding of the enlarged anticodon loop of tRNA1(Thr).
[Mh] Termos MeSH primário: Proteínas de Escherichia coli/metabolismo
RNA de Transferência de Treonina/metabolismo
Proteínas de Saccharomyces cerevisiae/metabolismo
Saccharomyces cerevisiae/metabolismo
Treonina-tRNA Ligase/metabolismo
[Mh] Termos MeSH secundário: Anticódon/química
Anticódon/genética
Anticódon/metabolismo
Sequência de Bases
Sítios de Ligação/genética
Cristalografia por Raios X
Proteínas de Escherichia coli/química
Proteínas de Escherichia coli/genética
Cinética
Mitocôndrias/genética
Mitocôndrias/metabolismo
Modelos Moleculares
Dados de Sequência Molecular
Conformação de Ácido Nucleico
Ligação Proteica
Estrutura Terciária de Proteína
RNA Fúngico/química
RNA Fúngico/genética
RNA Fúngico/metabolismo
RNA de Transferência de Treonina/química
RNA de Transferência de Treonina/genética
Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/química
Proteínas de Saccharomyces cerevisiae/genética
Treonina-tRNA Ligase/química
Treonina-tRNA Ligase/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Anticodon); 0 (Escherichia coli Proteins); 0 (RNA, Fungal); 0 (RNA, Transfer, Thr); 0 (Saccharomyces cerevisiae Proteins); EC 6.1.1.3 (MST1 protein, S cerevisiae); EC 6.1.1.3 (Threonine-tRNA Ligase)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151226
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkv1501


  9 / 191 MEDLINE  
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[PMID]:26464444
[Au] Autor:Rubio MÁ; Napolitano M; Ochoa de Alda JA; Santamaría-Gómez J; Patterson CJ; Foster AW; Bru-Martínez R; Robinson NJ; Luque I
[Ad] Endereço:Instituto de Bioquímica Vegetal y Fotosíntesis, C.S.I.C. and Universidad de Sevilla, Avda Américo Vespucio 49, E-41092 Seville, Spain.
[Ti] Título:Trans-oligomerization of duplicated aminoacyl-tRNA synthetases maintains genetic code fidelity under stress.
[So] Source:Nucleic Acids Res;43(20):9905-17, 2015 Nov 16.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Aminoacyl-tRNA synthetases (aaRSs) play a key role in deciphering the genetic message by producing charged tRNAs and are equipped with proofreading mechanisms to ensure correct pairing of tRNAs with their cognate amino acid. Duplicated aaRSs are very frequent in Nature, with 25,913 cases observed in 26,837 genomes. The oligomeric nature of many aaRSs raises the question of how the functioning and oligomerization of duplicated enzymes is organized. We characterized this issue in a model prokaryotic organism that expresses two different threonyl-tRNA synthetases, responsible for Thr-tRNA(Thr) synthesis: one accurate and constitutively expressed (T1) and another (T2) with impaired proofreading activity that also generates mischarged Ser-tRNA(Thr). Low zinc promotes dissociation of dimeric T1 into monomers deprived of aminoacylation activity and simultaneous induction of T2, which is active for aminoacylation under low zinc. T2 either forms homodimers or heterodimerizes with T1 subunits that provide essential proofreading activity in trans. These findings evidence that in organisms with duplicated genes, cells can orchestrate the assemblage of aaRSs oligomers that meet the necessities of the cell in each situation. We propose that controlled oligomerization of duplicated aaRSs is an adaptive mechanism that can potentially be expanded to the plethora of organisms with duplicated oligomeric aaRSs.
[Mh] Termos MeSH primário: Genes Duplicados
Treonina-tRNA Ligase/genética
Treonina-tRNA Ligase/metabolismo
[Mh] Termos MeSH secundário: Aminoacil-tRNA Sintetases/genética
Aminoacil-tRNA Sintetases/metabolismo
Anabaena/enzimologia
Anabaena/genética
Código Genético
Isoenzimas/genética
Isoenzimas/metabolismo
Multimerização Proteica
Edição de RNA
Estresse Fisiológico/genética
Zinco/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Isoenzymes); EC 6.1.1.- (Amino Acyl-tRNA Synthetases); EC 6.1.1.3 (Threonine-tRNA Ligase); J41CSQ7QDS (Zinc)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151015
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkv1020


  10 / 191 MEDLINE  
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[PMID]:25888844
[Au] Autor:De Langhe E; Lenaerts J; Bossuyt X; Westhovens R; Wuyts WA
[Ad] Endereço:Department of Rheumatology, University Hospitals Leuven, Herestraat 49, Leuven, 3000, Belgium. ellen.delanghe@uzleuven.be.
[Ti] Título:Mechanic's hands in a woman with undifferentiated connective tissue disease and interstitial lung disease--anti-PL7 positive antisynthetase syndrome: a case report.
[So] Source:J Med Case Rep;9:82, 2015 Apr 15.
[Is] ISSN:1752-1947
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Interstitial lung disease can be idiopathic or occur in the setting of connective tissue diseases. In the latter case it requires a different treatment approach with a better prognosis. Interstitial lung disease can precede the onset of typical connective tissue disease features by many years, and therefore meticulous multidisciplinary follow-up is crucial. This case highlights the diagnostic challenge and the need for intensified attention for subtle clinical features when faced with interstitial lung disease in patients with characteristics of a hitherto undifferentiated connective tissue disease. CASE PRESENTATION: A 44-year-old Caucasian woman presented to our pulmonology department with dyspnea, Raynaud's phenomenon and subtle swelling of fingers and eyelids. Laboratory analysis and autoantibody screening was negative. She was diagnosed with nonspecific interstitial pneumonia with a concurring undifferentiated connective tissue disease. After four years of stable disease, she presented with rapid pulmonary deterioration, myalgia, periorbital edema, arthritis and a cracked appearance of the radial sides of the fingers of both her hands. This clinical sign was recognized as mechanic's hands and a specific search for the presence of antisynthetase antibodies was performed. She was found to harbor anti-threonyl-tRNA synthetase antibodies. A diagnosis of antisynthetase syndrome was made and she was treated with glucocorticoids and immunosuppressives. CONCLUSIONS: This case highlights the difficulty in fine-tuning the diagnosis when confronted with a patient with interstitial lung disease and the suspicion of an underlying, yet undifferentiated connective tissue disease. There is a strong need for clinical multidisciplinary follow-up of these patients, with a high level of alertness to rare and specific clinical signs. The diagnosis of the underlying connective tissue disease profoundly influences the management of the interstitial lung disease. Recent data stress that identification of the autoantibody specificity allows for further prognostic stratification and therefore should be pursued.
[Mh] Termos MeSH primário: Doenças do Tecido Conjuntivo/diagnóstico
Imunossupressores/uso terapêutico
Doenças Pulmonares Intersticiais/diagnóstico
Miosite/diagnóstico
Treonina-tRNA Ligase/imunologia
[Mh] Termos MeSH secundário: Adulto
Autoanticorpos/sangue
Diagnóstico Tardio
Feminino
Mãos/patologia
Seres Humanos
Miosite/tratamento farmacológico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Autoantibodies); 0 (Immunosuppressive Agents); EC 6.1.1.3 (Threonine-tRNA Ligase)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:150424
[Lr] Data última revisão:
150424
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150419
[St] Status:MEDLINE
[do] DOI:10.1186/s13256-015-0571-2



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