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[PMID]:29185863
[Au] Autor:Martínez-Casares RM; Pérez Méndez HI; Manjarrez Alvarez N; Solís Oba A; Hernández Vázquez L; López-Luna A
[Ad] Endereço:a Doctorado en Ciencias Biológicas y de la Salud , Universidad Autónoma Metropolitana-Unidad Xochimilco , Coyoacán , CDMX , México.
[Ti] Título:Comparison of the diastereoisomeric excess of uridine, inosine and adenosine cyanohydrins determined by HPLC-DAD and H NMR.
[So] Source:Nucleosides Nucleotides Nucleic Acids;36(10):652-665, 2017 Oct 03.
[Is] ISSN:1532-2335
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The separation of the diastereoisomers of the nucleoside derivatives of uridine, inosine and adenosine was performed by HPLC using chiral and no chiral columns, it was observed with the no chiral columns the resolution was good enough to determine diastereoisomeric excess. These methods were compared with H NMR, and no significant differences were observed between the three techniques. Diastereoisomeric uridine (3a), inosine (3b) and adenosine (4c) cyanohydrins were resolved by H nuclear magnetic resonance ( H NMR), chiral normal phase-high-performance liquid chromatography-diode array detector (NP-HPLC-DAD) and reversed phase (RP-HPLC-DAD); these methods allowed the assesment of the percent diastereoisomeric excess (% de) of the nucleosidic cyanohydrins of 3a (4, 6 and 4), 3b (10, 8 and 6) and 4c (4, 4 and 4). To the best of our knowledge, there are no reports using analytical techniques for the separation of the epimers of 3a, 3b and 4c.
[Mh] Termos MeSH primário: Adenosina/química
Inosina/química
Nitrilos/química
Uridina/química
[Mh] Termos MeSH secundário: Cromatografia Líquida de Alta Pressão
Cromatografia de Fase Reversa
Espectroscopia de Ressonância Magnética
Estereoisomerismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Nitriles); 0 (cyanohydrin); 5A614L51CT (Inosine); K72T3FS567 (Adenosine); WHI7HQ7H85 (Uridine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171130
[St] Status:MEDLINE
[do] DOI:10.1080/15257770.2017.1375516


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[PMID]:29235978
[Au] Autor:Hakobyan A; Galindo I; Nañez A; Arabyan E; Karalyan Z; Chistov AA; Streshnev PP; Korshun VA; Alonso C; Zakaryan H
[Ad] Endereço:1​Group of Antiviral Defense Mechanisms, Institute of Molecular Biology of NAS RA, 0014, Yerevan, Armenia.
[Ti] Título:Rigid amphipathic fusion inhibitors demonstrate antiviral activity against African swine fever virus.
[So] Source:J Gen Virol;99(1):148-156, 2018 Jan.
[Is] ISSN:1465-2099
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Rigid amphipathic fusion inhibitors (RAFIs) are a family of nucleoside derivatives that inhibit the infectivity of several enveloped viruses by interacting with virion envelope lipids and inhibiting fusion between viral and cellular membranes. Here we tested the antiviral activity of two RAFIs, 5-(Perylen-3-ylethynyl)-arabino-uridine (aUY11) and 5-(Perylen-3-ylethynyl)uracil-1-acetic acid (cm1UY11) against African swine fever virus (ASFV), for which no effective vaccine is available. Both compounds displayed a potent, dose-dependent inhibitory effect on ASFV infection in Vero cells. The major antiviral effect was observed when aUY11 and cm1UY11 were added at early stages of infection and maintained during the complete viral cycle. Furthermore, virucidal assay revealed a significant extracellular anti-ASFV activity for both compounds. We also found decrease in the synthesis of early and late viral proteins in Vero cells treated with cm1UY11. Finally, the inhibitory effect of aUY11 and cm1UY11 on ASFV infection in porcine alveolar macrophages was confirmed. Overall, our study has identified novel anti-ASFV compounds with potential for future therapeutic developments.
[Mh] Termos MeSH primário: Vírus da Febre Suína Africana/efeitos dos fármacos
Antivirais/farmacologia
Perileno/análogos & derivados
Uracila/análogos & derivados
Uridina/análogos & derivados
Proteínas Virais/antagonistas & inibidores
Vírion/efeitos dos fármacos
Internalização do Vírus/efeitos dos fármacos
[Mh] Termos MeSH secundário: Vírus da Febre Suína Africana/crescimento & desenvolvimento
Vírus da Febre Suína Africana/metabolismo
Animais
Antivirais/síntese química
Membrana Celular/efeitos dos fármacos
Membrana Celular/virologia
Cercopithecus aethiops
Relação Dose-Resposta a Droga
Macrófagos Alveolares/efeitos dos fármacos
Macrófagos Alveolares/virologia
Testes de Sensibilidade Microbiana
Perileno/síntese química
Perileno/farmacologia
Cultura Primária de Células
Suínos
Uracila/síntese química
Uracila/farmacologia
Uridina/síntese química
Uridina/farmacologia
Células Vero
Proteínas Virais/biossíntese
Vírion/crescimento & desenvolvimento
Vírion/metabolismo
Replicação Viral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (5-(perylen-3-yl)ethynylarabinouridine); 0 (5-(perylen-3-ylethynyl)uracil-1-acetic acid); 0 (Antiviral Agents); 0 (Viral Proteins); 56HH86ZVCT (Uracil); 5QD5427UN7 (Perylene); WHI7HQ7H85 (Uridine)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171229
[Lr] Data última revisão:
171229
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE
[do] DOI:10.1099/jgv.0.000991


  3 / 11692 MEDLINE  
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[PMID]:28835346
[Au] Autor:Alexandre FR; Badaroux E; Bilello JP; Bot S; Bouisset T; Brandt G; Cappelle S; Chapron C; Chaves D; Convard T; Counor C; Da Costa D; Dukhan D; Gay M; Gosselin G; Griffon JF; Gupta K; Hernandez-Santiago B; La Colla M; Lioure MP; Milhau J; Paparin JL; Peyronnet J; Parsy C; Pierra Rouvière C; Rahali H; Rahali R; Salanson A; Seifer M; Serra I; Standring D; Surleraux D; Dousson CB
[Ad] Endereço:IDENIX an MSD Company, Cap Gamma, 1682 rue de la Valsière, 34189 Montpellier Cedex 4, France. Electronic address: francois-rene.alexandre@merck.com.
[Ti] Título:The discovery of IDX21437: Design, synthesis and antiviral evaluation of 2'-α-chloro-2'-ß-C-methyl branched uridine pronucleotides as potent liver-targeted HCV polymerase inhibitors.
[So] Source:Bioorg Med Chem Lett;27(18):4323-4330, 2017 09 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Herein we describe the discovery of IDX21437 35b, a novel R d-aminoacid-based phosphoramidate prodrug of 2'-α-chloro-2'-ß-C-methyluridine monophosphate. Its corresponding triphosphate 6 is a potent inhibitor of the HCV NS5B RNA-dependent RNA polymerase (RdRp). Despite showing very weak activity in the in vitro Huh-7 cell based HCV replicon assay, 35b demonstrated high levels of active triphosphate 6 in mouse liver and human hepatocytes. A biochemical study revealed that the metabolism of 35b was mainly attributed to carboxyesterase 1 (CES1), an enzyme which is underexpressed in HCV Huh-7-derived replicon cells. Furthermore, due to its metabolic activation, 35b was efficiently processed in liver cells compared to other cell types, including human cardiomyocytes. The selected R diastereoisomeric configuration of 35b was assigned by X-ray structural determination. 35b is currently in Phase II clinical trials for the treatment of HCV infection.
[Mh] Termos MeSH primário: Antivirais/farmacologia
RNA Polimerases Dirigidas por DNA/antagonistas & inibidores
Descoberta de Drogas
Inibidores Enzimáticos/farmacologia
Hepacivirus/efeitos dos fármacos
Uridina Monofosfato/análogos & derivados
Uridina/farmacologia
[Mh] Termos MeSH secundário: Animais
Antivirais/síntese química
Antivirais/química
RNA Polimerases Dirigidas por DNA/metabolismo
Relação Dose-Resposta a Droga
Inibidores Enzimáticos/síntese química
Inibidores Enzimáticos/química
Hepacivirus/enzimologia
Hepatócitos/efeitos dos fármacos
Hepatócitos/virologia
Seres Humanos
Fígado/efeitos dos fármacos
Fígado/virologia
Camundongos
Testes de Sensibilidade Microbiana
Estrutura Molecular
Relação Estrutura-Atividade
Uridina/síntese química
Uridina/química
Uridina Monofosfato/síntese química
Uridina Monofosfato/química
Uridina Monofosfato/farmacologia
Proteínas não Estruturais Virais/antagonistas & inibidores
Proteínas não Estruturais Virais/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Enzyme Inhibitors); 0 (IDX21437); 0 (NS-5 protein, hepatitis C virus); 0 (Viral Nonstructural Proteins); E2OU15WN0N (Uridine Monophosphate); EC 2.7.7.6 (DNA-Directed RNA Polymerases); WHI7HQ7H85 (Uridine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171125
[Lr] Data última revisão:
171125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170825
[St] Status:MEDLINE


  4 / 11692 MEDLINE  
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[PMID]:28768435
[Au] Autor:Galabov AS; Mukova L; Abashev YP; Wassilewa L; Tzvetkov P; Minkov V; Barinskiy IF; Rice CM; Ouzounov S; Sidzhakova D
[Ad] Endereço:1 The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
[Ti] Título:Cycluridine: A novel antiviral effective against flaviviruses.
[So] Source:Antivir Chem Chemother;25(2):58-67, 2017 Aug.
[Is] ISSN:2040-2066
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:This review describes the contemporary state of research for antivirals effective against flaviviruses, especially focusing on inhibitors of the pestivirus causative agent of bovine viral diarrhoea virus. We highlight cycluridine, an originally synthesized Mannich's base [a tetrahydro-2(1H)-pyrimidinones derivative], as a highly effective antiviral possessing a strong inhibitory effect on bovine viral diarrhoea virus replication. Cycluridine was active against replication of a wide variety of bovine viral diarrhoea virus strains in cell cultures. The drug-sensitive period in the bovine viral diarrhoea virus replication cycle included the latent period and the exponential phase; a 90-min delay in the peak of viral RNA synthesis was observed. Cycluridine administered orally manifested a pronounced protective effect in calves with natural mucosal disease/viral diarrhoea and calves experimentally infected with bovine viral diarrhoea virus. Its magnitude of activity and selectivity places cycluridine in the lead among all known substances with anti- bovine viral diarrhoea virus activity. Additionally, cycluridine applied subcutaneously showed anti-tick-born encephalitis virus activity, manifesting a marked protective effect in mice infected with tick-born encephalitis virus. Cycluridine could be a prospective antiviral in veterinary and medical practice for the treatment of bovine viral diarrhoea virus and other flavivirus infections.
[Mh] Termos MeSH primário: Antivirais/farmacologia
Flavivirus/efeitos dos fármacos
Uridina/farmacologia
[Mh] Termos MeSH secundário: Animais
Antivirais/química
Antivirais/uso terapêutico
Flavivirus/fisiologia
Infecções por Flavivirus/tratamento farmacológico
Seres Humanos
Uridina/química
Uridina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antiviral Agents); WHI7HQ7H85 (Uridine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170811
[Lr] Data última revisão:
170811
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE
[do] DOI:10.1177/2040206617723442


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[PMID]:28661652
[Au] Autor:Stecula A; Schlessinger A; Giacomini KM; Sali A
[Ad] Endereço:Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco , San Francisco, California 94158, United States.
[Ti] Título:Human Concentrative Nucleoside Transporter 3 (hCNT3, SLC28A3) Forms a Cyclic Homotrimer.
[So] Source:Biochemistry;56(27):3475-3483, 2017 Jul 11.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Many anticancer and antiviral drugs are purine or pyrimidine analogues, which use membrane transporters to cross cellular membranes. Concentrative nucleoside transporters (CNTs) mediate the salvage of nucleosides and the transport of therapeutic nucleoside analogues across plasma membranes by coupling the transport of ligands to the sodium gradient. Of the three members of the human CNT family, CNT3 has the broadest selectivity and the widest expression profile. However, the molecular mechanisms of the transporter, including how it interacts with and translocates structurally diverse nucleosides and nucleoside analogues, are unclear. Recently, the crystal structure of vcCNT showed that the prokaryotic homologue of CNT3 forms a homotrimer. In this study, we successfully expressed and purified the wild type human homologue, hCNT3, demonstrating the homotrimer by size exclusion profiles and glutaraldehyde cross-linking. Further, by creating a series of cysteine mutants at highly conserved positions guided by comparative structure models, we cross-linked hCNT3 protomers in a cell-based assay, thus showing the existence of hCNT3 homotrimers in human cells. The presence and absence of cross-links at specific locations along TM9 informs us of important structural differences between vcCNT and hCNT3. Comparative modeling of the trimerization domain and sequence coevolution analysis both indicate that oligomerization is critical to the stability and function of hCNT3. In particular, trimerization appears to shorten the translocation path for nucleosides across the plasma membrane and may allow modulation of the transport function via allostery.
[Mh] Termos MeSH primário: Proteínas de Membrana Transportadoras/química
Modelos Moleculares
[Mh] Termos MeSH secundário: Absorção Fisiológica
Animais
Linhagem Celular
Cromatografia em Gel
Simulação por Computador
Reagentes para Ligações Cruzadas/química
Glutaral/química
Seres Humanos
Bicamadas Lipídicas/química
Bicamadas Lipídicas/metabolismo
Proteínas de Membrana Transportadoras/genética
Proteínas de Membrana Transportadoras/metabolismo
Conformação Molecular
Peso Molecular
Mutagênese Sítio-Dirigida
Mutação
Domínios e Motivos de Interação entre Proteínas
Estrutura Quaternária de Proteína
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/metabolismo
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Sus scrofa
Trítio
Uridina/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cross-Linking Reagents); 0 (Lipid Bilayers); 0 (Membrane Transport Proteins); 0 (Recombinant Fusion Proteins); 0 (Recombinant Proteins); 0 (cif nucleoside transporter); 10028-17-8 (Tritium); T3C89M417N (Glutaral); WHI7HQ7H85 (Uridine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170726
[Lr] Data última revisão:
170726
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170630
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00339


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[PMID]:28617590
[Au] Autor:Chen JL; VanEtten DM; Fountain MA; Yildirim I; Disney MD
[Ad] Endereço:Department of Chemistry, The Scripps Research Institute , Jupiter, Florida 33458, United States.
[Ti] Título:Structure and Dynamics of RNA Repeat Expansions That Cause Huntington's Disease and Myotonic Dystrophy Type 1.
[So] Source:Biochemistry;56(27):3463-3474, 2017 Jul 11.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RNA repeat expansions cause a host of incurable, genetically defined diseases. The most common class of RNA repeats consists of trinucleotide repeats. These long, repeating transcripts fold into hairpins containing 1 × 1 internal loops that can mediate disease via a variety of mechanism(s) in which RNA is the central player. Two of these disorders are Huntington's disease and myotonic dystrophy type 1, which are caused by r(CAG) and r(CUG) repeats, respectively. We report the structures of two RNA constructs containing three copies of a r(CAG) [r(3×CAG)] or r(CUG) [r(3×CUG)] motif that were modeled with nuclear magnetic resonance spectroscopy and simulated annealing with restrained molecular dynamics. The 1 × 1 internal loops of r(3×CAG) are stabilized by one-hydrogen bond (cis Watson-Crick/Watson-Crick) AA pairs, while those of r(3×CUG) prefer one- or two-hydrogen bond (cis Watson-Crick/Watson-Crick) UU pairs. Assigned chemical shifts for the residues depended on the identity of neighbors or next nearest neighbors. Additional insights into the dynamics of these RNA constructs were gained by molecular dynamics simulations and a discrete path sampling method. Results indicate that the global structures of the RNA are A-form and that the loop regions are dynamic. The results will be useful for understanding the dynamic trajectory of these RNA repeats but also may aid in the development of therapeutics.
[Mh] Termos MeSH primário: Proteína Huntingtina/genética
Doença de Huntington/genética
Modelos Moleculares
Distrofia Miotônica/genética
Miotonina Proteína Quinase/genética
RNA Mensageiro/química
Expansão das Repetições de Trinucleotídeos
[Mh] Termos MeSH secundário: Regiões 3' não Traduzidas
Pareamento de Bases
Transferência de Energia
Éxons
Seres Humanos
Proteína Huntingtina/química
Proteína Huntingtina/metabolismo
Doença de Huntington/metabolismo
Ligações de Hidrogênio
Simulação de Dinâmica Molecular
Mutação
Distrofia Miotônica/metabolismo
Miotonina Proteína Quinase/química
Miotonina Proteína Quinase/metabolismo
Ressonância Magnética Nuclear Biomolecular
Conformação de Ácido Nucleico
Motivos de Nucleotídeos
Dobramento de RNA
RNA Mensageiro/metabolismo
Uridina/análogos & derivados
Uridina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3' Untranslated Regions); 0 (DMPK protein, human); 0 (HTT protein, human); 0 (Huntingtin Protein); 0 (RNA, Messenger); 4K0M952561 (5-fluorouridine); EC 2.7.11.1 (Myotonin-Protein Kinase); WHI7HQ7H85 (Uridine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170726
[Lr] Data última revisão:
170726
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170616
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00252


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[PMID]:28549193
[Au] Autor:Glasner H; Riml C; Micura R; Breuker K
[Ad] Endereço:Institute of Organic Chemistry and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
[Ti] Título:Label-free, direct localization and relative quantitation of the RNA nucleobase methylations m6A, m5C, m3U, and m5U by top-down mass spectrometry.
[So] Source:Nucleic Acids Res;45(13):8014-8025, 2017 Jul 27.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Nucleobase methylations are ubiquitous posttranscriptional modifications of ribonucleic acids (RNA) that can substantially increase the structural diversity of RNA in a highly dynamic fashion with implications for gene expression and human disease. However, high throughput, deep sequencing does not generally provide information on posttranscriptional modifications (PTMs). A promising alternative approach for the characterization of PTMs, i.e. their identification, localization, and relative quantitation, is top-down mass spectrometry (MS). In this study, we have investigated how specific nucleobase methylations affect RNA ionization in electrospray ionization (ESI), and backbone cleavage in collisionally activated dissociation (CAD) and electron detachment dissociation (EDD). For this purpose, we have developed two new approaches for the characterization of RNA methylations in mixtures of either isomers of RNA or nonisomeric RNA forms. Fragment ions from dissociation experiments were analyzed to identify the modification type, to localize the modification sites, and to reveal the site-specific, relative extent of modification for each site.
[Mh] Termos MeSH primário: RNA/química
Espectrometria de Massas por Ionização por Electrospray/métodos
[Mh] Termos MeSH secundário: Adenosina/análogos & derivados
Adenosina/análise
Adenosina/química
Sequência de Bases
Citidina/análogos & derivados
Citidina/análise
Citidina/química
Íons
Metilação
Estrutura Molecular
Espectroscopia de Infravermelho com Transformada de Fourier/métodos
Uridina/análogos & derivados
Uridina/análise
Uridina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ions); 1463-10-1 (ribothymidine); 1867-73-8 (N(6)-methyladenosine); 2140-69-4 (3-methyluridine); 5CSZ8459RP (Cytidine); 63231-63-0 (RNA); K72T3FS567 (Adenosine); TL9PB228DC (5-methylcytidine); WHI7HQ7H85 (Uridine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170527
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx470


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[PMID]:28472077
[Au] Autor:Fan X; Wu H; Li G; Yuan H; Zhang H; Li Y; Xie X; Chen N
[Ad] Endereço:National and Local United Engineering Lab of Metabolic Control Fermentation Technology, Tianjin University of Science and Technology, Tianjin, P. R. China.
[Ti] Título:Improvement of uridine production of Bacillus subtilis by atmospheric and room temperature plasma mutagenesis and high-throughput screening.
[So] Source:PLoS One;12(5):e0176545, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In the present study, a novel breeding strategy of atmospheric and room temperature plasma (ARTP) mutagenesis was used to improve the uridine production of engineered Bacillus subtilis TD12np. A high-throughput screening method was established using both resistant plates and 96-well microplates to select the ideal mutants with diverse phenotypes. Mutant F126 accumulated 5.7 and 30.3 g/L uridine after 30 h in shake-flask and 48 h in fed-batch fermentation, respectively, which represented a 4.4- and 8.7-fold increase over the parent strain. Sequence analysis of the pyrimidine nucleotide biosynthetic operon in the representative mutants showed that proline 1016 and glutamate 949 in the large subunit of B. subtilis carbamoyl phosphate synthetase were of importance for the allosteric regulation caused by uridine 5'-monophosphate. The proposed mutation method with efficient high-throughput screening assay was proved to be an appropriate strategy to obtain uridine-overproducing strain.
[Mh] Termos MeSH primário: Bacillus subtilis/metabolismo
Ensaios de Triagem em Larga Escala
Mutagênese
Uridina/biossíntese
[Mh] Termos MeSH secundário: Bacillus subtilis/genética
Sequência de Bases
Fermentação
Homologia de Sequência do Ácido Nucleico
Temperatura Ambiente
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
WHI7HQ7H85 (Uridine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170908
[Lr] Data última revisão:
170908
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0176545


  9 / 11692 MEDLINE  
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[PMID]:28430781
[Au] Autor:Nilsson K; Jäger G; Björk GR
[Ad] Endereço:Department of Molecular Biology, Umeå University, Umeå, Sweden.
[Ti] Título:An unmodified wobble uridine in tRNAs specific for Glutamine, Lysine, and Glutamic acid from Salmonella enterica Serovar Typhimurium results in nonviability-Due to increased missense errors?
[So] Source:PLoS One;12(4):e0175092, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In the wobble position of tRNAs specific for Gln, Lys, and Glu a universally conserved 5-methylene-2-thiouridine derivative (xm5s2U34, x denotes any of several chemical substituents and 34 denotes the wobble position) is present, which is 5-(carboxy)methylaminomethyl-2-thiouridine ((c)mnm5s2U34) in Bacteria and 5-methylcarboxymethyl-2-thiouridine (mcm5s2U34) in Eukarya. Here we show that mutants of the bacterium Salmonella enterica Serovar Typhimurium LT2 lacking either the s2- or the (c)mnm5-group of (c)mnm5s2U34 grow poorly especially at low temperature and do not grow at all at 15°C in both rich and glucose minimal media. A double mutant of S. enterica lacking both the s2- and the (c)mnm5-groups, and that thus has an unmodified uridine as wobble nucleoside, is nonviable at different temperatures. Overexpression of [Formula: see text] lacking either the s2- or the (c)mnm5-group and of [Formula: see text] lacking the s2-group exaggerated the reduced growth induced by the modification deficiency, whereas overexpression of [Formula: see text] lacking the mnm5-group did not. From these results we suggest that the primary function of cmnm5s2U34 in bacterial [Formula: see text] and mnm5s2U34 in [Formula: see text] is to prevent missense errors, but the mnm5-group of [Formula: see text] does not. However, other translational errors causing the growth defect cannot be excluded. These results are in contrast to what is found in yeast, since overexpression of the corresponding hypomodified yeast tRNAs instead counteracts the modification deficient induced phenotypes. Accordingly, it was suggested that the primary function of mcm5s2U34 in these yeast tRNAs is to improve cognate codon reading rather than prevents missense errors. Thus, although the xm5s2U34 derivatives are universally conserved, their major functional impact on bacterial and eukaryotic tRNAs may be different.
[Mh] Termos MeSH primário: Ácido Glutâmico/genética
Glutamina/genética
Lisina/genética
Mutação de Sentido Incorreto
RNA de Transferência/genética
Salmonella typhimurium/genética
Uridina/genética
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0RH81L854J (Glutamine); 3KX376GY7L (Glutamic Acid); 9014-25-9 (RNA, Transfer); K3Z4F929H6 (Lysine); WHI7HQ7H85 (Uridine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170422
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0175092


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[PMID]:28424521
[Au] Autor:Hirschi M; Johnson ZL; Lee SY
[Ad] Endereço:Department of Biochemistry, Duke University Medical Center, 303 Research Drive, Durham, North Carolina 27710, USA.
[Ti] Título:Visualizing multistep elevator-like transitions of a nucleoside transporter.
[So] Source:Nature;545(7652):66-70, 2017 05 04.
[Is] ISSN:1476-4687
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Membrane transporters move substrates across the membrane by alternating access of their binding sites between the opposite sides of the membrane. An emerging model of this process is the elevator mechanism, in which a substrate-binding transport domain moves a large distance across the membrane. This mechanism has been characterized by a transition between two states, but the conformational path that leads to the transition is not yet known, largely because the available structural information has been limited to the two end states. Here we present crystal structures of the inward-facing, intermediate, and outward-facing states of a concentrative nucleoside transporter from Neisseria wadsworthii. Notably, we determined the structures of multiple intermediate conformations, in which the transport domain is captured halfway through its elevator motion. Our structures present a trajectory of the conformational transition in the elevator model, revealing multiple intermediate steps and state-dependent conformational changes within the transport domain that are associated with the elevator-like motion.
[Mh] Termos MeSH primário: Modelos Biológicos
Movimento
Neisseria/química
Proteínas de Transporte de Nucleosídeos/química
Proteínas de Transporte de Nucleosídeos/metabolismo
[Mh] Termos MeSH secundário: Sítios de Ligação
Cristalização
Cristalografia por Raios X
Cisteína/química
Cisteína/metabolismo
Elevadores e Escadas Rolantes
Ligantes
Modelos Moleculares
Mutação
Domínios Proteicos
Uridina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Ligands); 0 (Nucleoside Transport Proteins); K848JZ4886 (Cysteine); WHI7HQ7H85 (Uridine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170421
[St] Status:MEDLINE
[do] DOI:10.1038/nature22057



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