Base de dados : MEDLINE
Pesquisa : D03.383.663.283.446.139 [Categoria DeCS]
Referências encontradas : 241 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 25 ir para página                         

  1 / 241 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27376828
[Au] Autor:Cele FN; Kumalo H; Soliman ME
[Ad] Endereço:Molecular Modelling and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, 4001, South Africa.
[Ti] Título:Mechanism of Inhibition of Hsp90 Dimerization by Gyrase B Inhibitor Coumermycin A1 (C-A1) Revealed by Molecular Dynamics Simulations and Thermodynamic Calculations.
[So] Source:Cell Biochem Biophys;74(3):353-63, 2016 Sep.
[Is] ISSN:1559-0283
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Heat shock protein (Hsp) 90 an emerging and attracting target in the anti-HIV drug discovery process due to the key role it plays in the pathogenicity of HIV-1 virus. In this research study, long-range all-atom molecular dynamics simulations were engaged for the bound and the unbound proteins to enhance the understanding of the molecular mechanisms of the Hsp90 dimerization and inhibition. Results evidently showed that coumermycin A1 (C-A1), a recently discovered Hsp90 inhibitor, binds at the dimer's active site of the Hsp90 protein and leads to a substantial parting between dimeric opposed residues, which include Arg591.B, Lys594.A, Ser663.A, Thr653.B, Ala665.A, Thr649.B, Leu646.B and Asn669.A. Significant differences in magnitudes were observed in radius of gyration, root-mean-square deviation and root-mean-square fluctuation, which confirms a reasonably more flexible state in the apo conformation associated with it dimerization. In contrast, the bound conformer of Hsp90 showed less flexibility. This visibly highpoints the inhibition process resulting from the binding of the ligand. These findings were further validated by principal component analysis. We believe that the detailed dynamic analyses of Hsp90 presented in this study, would give an imperative insight and better understanding to the function and mechanisms of inhibition. Furthermore, information obtained from the binding mode of the inhibitor would be of great assistance in the design of more potent inhibitors against the HIV target Hsp90.
[Mh] Termos MeSH primário: Aminocumarinas/metabolismo
Proteínas de Choque Térmico HSP90/metabolismo
[Mh] Termos MeSH secundário: Aminocumarinas/química
Sítios de Ligação
Dimerização
Proteínas de Choque Térmico HSP90/antagonistas & inibidores
Simulação de Dinâmica Molecular
Análise de Componente Principal
Ligação Proteica
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aminocoumarins); 0 (HSP90 Heat-Shock Proteins); PCH9QZ1IIH (coumermycin)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170119
[Lr] Data última revisão:
170119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160705
[St] Status:MEDLINE
[do] DOI:10.1007/s12013-016-0743-8


  2 / 241 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:27107820
[Au] Autor:Chen NY; Zhou L; Gane PJ; Opp S; Ball NJ; Nicastro G; Zufferey M; Buffone C; Luban J; Selwood D; Diaz-Griffero F; Taylor I; Fassati A
[Ad] Endereço:Division of Infection and Immunity, University College London, Cruciform Building, 90 Gower Street, London, WC1E 6BT, UK.
[Ti] Título:HIV-1 capsid is involved in post-nuclear entry steps.
[So] Source:Retrovirology;13:28, 2016 Apr 23.
[Is] ISSN:1742-4690
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: HIV-1 capsid influences viral uncoating and nuclear import. Some capsid is detected in the nucleus but it is unclear if it has any function. We reported that the antibiotic Coumermycin-A1 (C-A1) inhibits HIV-1 integration and that a capsid mutation confers resistance to C-A1, suggesting that capsid might affect post-nuclear entry steps. RESULTS: Here we report that C-A1 inhibits HIV-1 integration in a capsid-dependent way. Using molecular docking, we identify an extended binding pocket delimited by two adjacent capsid monomers where C-A1 is predicted to bind. Isothermal titration calorimetry confirmed that C-A1 binds to hexameric capsid. Cyclosporine washout assays in Jurkat CD4+ T cells expressing engineered human TRIMCyp showed that C-A1 causes faster and greater escape from TRIMCyp restriction. Sub-cellular fractionation showed that small amounts of capsid accumulated in the nuclei of infected cells and C-A1 reduced the nuclear capsid. A105S and N74D capsid mutant viruses did not accumulate capsid in the nucleus, irrespective of C-A1 treatment. Depletion of Nup153, a nucleoporin located at the nuclear side of the nuclear pore that binds to HIV-1 capsid, made the virus less susceptible to TRIMCyp restriction, suggesting that Nup153 may help maintain some integrity of the viral core in the nucleus. Furthermore C-A1 increased binding of CPSF6, a nuclear protein, to capsid. CONCLUSIONS: Our results indicate that capsid is involved in post-nuclear entry steps preceding integration.
[Mh] Termos MeSH primário: Proteína do Núcleo p24 do HIV/metabolismo
HIV-1/fisiologia
Internalização do Vírus
[Mh] Termos MeSH secundário: Aminocumarinas/metabolismo
Antivirais/metabolismo
Linhagem Celular
HIV-1/efeitos dos fármacos
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Aminocoumarins); 0 (Antiviral Agents); 0 (HIV Core Protein p24); PCH9QZ1IIH (coumermycin)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160425
[St] Status:MEDLINE
[do] DOI:10.1186/s12977-016-0262-0


  3 / 241 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27060564
[Au] Autor:Coelho J; Ferreira F; Martins C; Leitão A
[Ad] Endereço:CIISA, Faculdade de Medicina Veterinária, ULisboa, Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal. Electronic address: jnscoelho@gmail.com.
[Ti] Título:Functional characterization and inhibition of the type II DNA topoisomerase coded by African swine fever virus.
[So] Source:Virology;493:209-16, 2016 Jun.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:DNA topoisomerases are essential for DNA metabolism and while their role is well studied in prokaryotes and eukaryotes, it is less known for virally-encoded topoisomerases. African swine fever virus (ASFV) is a nucleo-cytoplasmic large DNA virus that infects Ornithodoros ticks and all members of the family Suidae, representing a global threat for pig husbandry with no effective vaccine nor treatment. It was recently demonstrated that ASFV codes for a type II topoisomerase, highlighting a possible target for control of the virus. In this work, the ASFV DNA topoisomerase II was expressed in Saccharomyces cerevisiae and found to efficiently decatenate kDNA and to processively relax supercoiled DNA. Optimal conditions for its activity were determined and its sensitivity to a panel of topoisomerase poisons and inhibitors was evaluated. Overall, our results provide new knowledge on viral topoisomerases and on ASFV, as well as a possible target for the control of this virus.
[Mh] Termos MeSH primário: Vírus da Febre Suína Africana/enzimologia
DNA Topoisomerases Tipo II/genética
Inibidores da Topoisomerase II/farmacologia
[Mh] Termos MeSH secundário: Vírus da Febre Suína Africana/genética
Aminocumarinas/farmacologia
Amsacrina/farmacologia
Crithidia fasciculata/genética
Doxorrubicina/farmacologia
Saccharomyces cerevisiae/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aminocoumarins); 0 (Topoisomerase II Inhibitors); 00DPD30SOY (Amsacrine); 80168379AG (Doxorubicin); EC 5.99.1.3 (DNA Topoisomerases, Type II); PCH9QZ1IIH (coumermycin)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170509
[Lr] Data última revisão:
170509
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160410
[St] Status:MEDLINE


  4 / 241 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27037933
[Au] Autor:Byrd KM; Subramanian C; Sanchez J; Motiwala HF; Liu W; Cohen MS; Holzbeierlein J; Blagg BS
[Ad] Endereço:Department of Medicinal Chemistry, The University of Kansas, Wescoe Hall Drive, Malott 4070, Lawrence, KS, 66045-7563, USA.
[Ti] Título:Synthesis and Biological Evaluation of Novobiocin Core Analogues as Hsp90 Inhibitors.
[So] Source:Chemistry;22(20):6921-31, 2016 05 10.
[Is] ISSN:1521-3765
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Development of heat shock protein 90 (Hsp90) C-terminal inhibitors has emerged as an exciting strategy for the treatment of cancer. Previous efforts have focused on modifications to the natural products novobiocin and coumermycin. Moreover, variations in both the sugar and amide moieties have been extensively studied, whereas replacements for the coumarin core have received less attention. Herein, 24 cores were synthesized with varying distances and angles between the sugar and amide moieties. Compounds that exhibited good anti-proliferative activity against multiple cancer cell lines and Hsp90 inhibitory activity, were those that placed the sugar and amide moieties between 7.7 and 12.1 Šapart along with angles of 180°.
[Mh] Termos MeSH primário: Antineoplásicos/síntese química
Antineoplásicos/farmacologia
Proteínas de Choque Térmico HSP90/antagonistas & inibidores
Proteínas de Choque Térmico HSP90/química
Novobiocina/análogos & derivados
[Mh] Termos MeSH secundário: Aminocumarinas/química
Antineoplásicos/química
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Técnicas de Química Sintética
Cumarínicos/química
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Estrutura Molecular
Novobiocina/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Aminocoumarins); 0 (Antineoplastic Agents); 0 (Coumarins); 0 (HSP90 Heat-Shock Proteins); 17EC19951N (Novobiocin); A4VZ22K1WT (coumarin); PCH9QZ1IIH (coumermycin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170614
[Lr] Data última revisão:
170614
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160403
[St] Status:MEDLINE
[do] DOI:10.1002/chem.201504955


  5 / 241 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26637421
[Au] Autor:Wolanski M; Lebkowski T; Kois-Ostrowska A; Zettler J; Apel AK; Jakimowicz D; Zakrzewska-Czerwinska J
[Ad] Endereço:Faculty of Biotechnology, University of Wroclaw, ul. Joliot-Curie 14A, 50-383, Wroclaw, Poland. marcin.wolanski@uni.wroc.pl.
[Ti] Título:Two transcription factors, CabA and CabR, are independently involved in multilevel regulation of the biosynthetic gene cluster encoding the novel aminocoumarin, cacibiocin.
[So] Source:Appl Microbiol Biotechnol;100(7):3147-64, 2016 Apr.
[Is] ISSN:1432-0614
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Aminocoumarins are potent antibiotics belonging to a relatively small group of secondary metabolites produced by actinomycetes. Genome mining of Catenulispora acidiphila has recently led to the discovery of a gene cluster responsible for biosynthesis of novel aminocoumarins, cacibiocins. However, regulation of the expression of this novel gene cluster has not yet been analyzed. In this study, we identify transcriptional regulators of the cacibiocin gene cluster. Using a heterologous expression system, we show that the CabA and CabR proteins encoded by cabA and cabR genes in the cacibiocin gene cluster control the expression of genes involved in the biosynthesis, modification, regulation, and potentially, efflux/resistance of cacibiocins. CabA positively regulates the expression of cabH (the first gene in the cabHIYJKL operon) and cabhal genes encoding key enzymes responsible for the biosynthesis and halogenation of the aminocoumarin moiety, respectively. We provide evidence that CabA is a direct inducer of cacibiocin production, whereas the second transcriptional factor, CabR, is involved in the negative regulation of its own gene and cabT-the latter of which encodes a putative cacibiocin transporter. We also demonstrate that CabR activity is negatively regulated in vitro by aminocoumarin compounds, suggesting the existence of analogous regulation in vivo. Finally, we propose a model of multilevel regulation of gene transcription in the cacibiocin gene cluster by CabA and CabR.
[Mh] Termos MeSH primário: Actinomycetales/genética
Aminocumarinas/metabolismo
Antibacterianos/biossíntese
Proteínas de Bactérias/genética
Genes Bacterianos
Genoma Bacteriano
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: Actinomycetales/química
Actinomycetales/metabolismo
Sequência de Aminoácidos
Aminocumarinas/química
Antibacterianos/química
Proteínas de Bactérias/metabolismo
Sequência de Bases
Clonagem Molecular
Farmacorresistência Bacteriana
Escherichia coli/genética
Escherichia coli/metabolismo
Expressão Gênica
Regulação Bacteriana da Expressão Gênica
Família Multigênica
Óperon
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Alinhamento de Sequência
Streptomyces coelicolor/genética
Streptomyces coelicolor/metabolismo
Fatores de Transcrição/metabolismo
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Aminocoumarins); 0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (Recombinant Proteins); 0 (Transcription Factors)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151206
[St] Status:MEDLINE
[do] DOI:10.1007/s00253-015-7196-7


  6 / 241 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26308867
[Au] Autor:Roubinet B; Massif C; Moreau M; Boschetti F; Ulrich G; Ziessel R; Renard PY; Romieu A
[Ad] Endereço:Normandie Université, COBRA UMR 6014 & FR 3035, UNIV Rouen; INSA Rouen; CNRS, IRCOF, 1, Rue Tesnières, 76821 Mont-Saint-Aignan cedex (France), Fax: (+33) 2-35-52-29-71 http://ircof.crihan.fr.
[Ti] Título:New 3-(heteroaryl)-2-iminocoumarin-based borate complexes: synthesis, photophysical properties, and rational functionalization for biosensing/biolabeling applications.
[So] Source:Chemistry;21(41):14589-601, 2015 Oct 05.
[Is] ISSN:1521-3765
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Members of a series of boron difluoride complexes with 3-(heteroaryl)-2-iminocoumarin ligands bearing both a phenolic hydroxyl group (acting as a fluorogenic center) and an N-aryl substituent (acting as a stabilizing moiety) have been synthesized in good yields by applying a straightforward two-step method. These novel fluorogenic dyes belong to the family of "Boricos" (D. Frath et al., Chem. Commun.- 2013, 49, 4908-4910) and are the first examples of phenol-based fluorophores of which the photophysical properties in the green-yellow spectral range are dramatically improved by N,N-chelation of a boron atom. Modulation of their fluorescence properties through reversible chemical modification of their phenol moieties has been demonstrated by the preparation of the corresponding 2,4-dinitrophenyl (DNP) ethers, which led to a dramatic "OFF-ON" fluorescence response upon reaction with thiols. Additionally, to expand the scope of these "7-hydroxy-Borico" derivatives, particularly in biolabeling, amine or carboxylic acid functionalities amenable to (bio)conjugation have been introduced within their scaffold. Their utility has been demonstrated in the preparation of fluorescent bovine serum albumin (BSA) conjugates and "Borico"-DOTA-like scaffolds in an effort to design novel monomolecular multimodal fluorescence- radioisotope imaging agents.
[Mh] Termos MeSH primário: Aminocumarinas/química
Aminocumarinas/síntese química
Boratos/síntese química
Compostos de Boro/química
Compostos de Boro/síntese química
Cumarínicos/química
Cumarínicos/síntese química
Corantes Fluorescentes/química
Compostos Macrocíclicos/química
Soroalbumina Bovina/química
[Mh] Termos MeSH secundário: Boratos/química
Ligantes
Estrutura Molecular
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (7-hydroxy-boron(III)iminocoumarin); 0 (Aminocoumarins); 0 (Borates); 0 (Boron Compounds); 0 (Coumarins); 0 (Fluorescent Dyes); 0 (Ligands); 0 (Macrocyclic Compounds); 27432CM55Q (Serum Albumin, Bovine)
[Em] Mês de entrada:1605
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150827
[St] Status:MEDLINE
[do] DOI:10.1002/chem.201502126


  7 / 241 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:26239981
[Au] Autor:Jacoby GA; Corcoran MA; Hooper DC
[Ad] Endereço:Lahey Hospital and Medical Center, Burlington, Massachusetts, USA gajacoby50@gmail.com.
[Ti] Título:Protective effect of Qnr on agents other than quinolones that target DNA gyrase.
[So] Source:Antimicrob Agents Chemother;59(11):6689-95, 2015 Nov.
[Is] ISSN:1098-6596
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Qnr is a plasmid-encoded and chromosomally determined protein that protects DNA gyrase and topoisomerase IV from inhibition by quinolones. Despite its prevalence worldwide and existence prior to the discovery of quinolones, its native function is not known. Other synthetic compounds and natural products also target bacterial topoisomerases. A number were studied as molecular probes to gain insight into how Qnr acts. Qnr blocked inhibition by synthetic compounds with somewhat quinolone-like structure that target the GyrA subunit, such as the 2-pyridone ABT-719, the quinazoline-2,4-dione PD 0305970, and the spiropyrimidinetrione pyrazinyl-alkynyl-tetrahydroquinoline (PAT), indicating that Qnr is not strictly quinolone specific, but Qnr did not protect against GyrA-targeting simocyclinone D8 despite evidence that both simocyclinone D8 and Qnr affect DNA binding to gyrase. Qnr did not affect the activity of tricyclic pyrimidoindole or pyrazolopyridones, synthetic inhibitors of the GyrB subunit, or nonsynthetic GyrB inhibitors, such as coumermycin A1, novobiocin, gyramide A, or microcin B17.Thus, in this set of compounds the protective activity of Qnr was confined to those that, like quinolones, trap gyrase on DNA in cleaved complexes.
[Mh] Termos MeSH primário: DNA Girase/metabolismo
Proteínas de Escherichia coli/metabolismo
Escherichia coli/efeitos dos fármacos
Escherichia coli/enzimologia
Quinolonas/farmacologia
[Mh] Termos MeSH secundário: Aminocumarinas
Bacteriocinas/farmacologia
Escherichia coli/genética
Proteínas de Escherichia coli/genética
Novobiocina/farmacologia
Piridonas/farmacologia
Pirrolidinas/farmacologia
Quinazolinonas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (3-amino-7-(3-(1-aminoethyl)pyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-8-methyl-1H-quinazoline-2,4-dione); 0 (ABT 719); 0 (Aminocoumarins); 0 (Bacteriocins); 0 (Escherichia coli Proteins); 0 (Pyridones); 0 (Pyrrolidines); 0 (Qnr protein, E coli); 0 (Quinazolinones); 0 (Quinolones); 0 (gyramide A); 1403-96-9 (microcin); 17EC19951N (Novobiocin); EC 5.99.1.3 (DNA Gyrase); PCH9QZ1IIH (coumermycin)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150805
[St] Status:MEDLINE
[do] DOI:10.1128/AAC.01292-15


  8 / 241 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:25751579
[Au] Autor:Schimer J; Pávová M; Anders M; Pachl P; Sácha P; Cígler P; Weber J; Majer P; Rezácová P; Kräusslich HG; Müller B; Konvalinka J
[Ad] Endereço:1] Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences and IOCB Research Center, Flemingovo n.2, 166 10, Prague 6, Czech Republic [2] Department of Biochemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 128 43, Prague 2, Cze
[Ti] Título:Triggering HIV polyprotein processing by light using rapid photodegradation of a tight-binding protease inhibitor.
[So] Source:Nat Commun;6:6461, 2015 Mar 09.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:HIV protease (PR) is required for proteolytic maturation in the late phase of HIV replication and represents a prime therapeutic target. The regulation and kinetics of viral polyprotein processing and maturation are currently not understood in detail. Here we design, synthesize, validate and apply a potent, photodegradable HIV PR inhibitor to achieve synchronized induction of proteolysis. The compound exhibits subnanomolar inhibition in vitro. Its photolabile moiety is released on light irradiation, reducing the inhibitory potential by 4 orders of magnitude. We determine the structure of the PR-inhibitor complex, analyze its photolytic products, and show that the enzymatic activity of inhibited PR can be fully restored on inhibitor photolysis. We also demonstrate that proteolysis of immature HIV particles produced in the presence of the inhibitor can be rapidly triggered by light enabling thus to analyze the timing, regulation and spatial requirements of viral processing in real time.
[Mh] Termos MeSH primário: Aminocumarinas/farmacologia
Carbamatos/farmacologia
Inibidores da Protease de HIV/farmacologia
Protease de HIV/química
HIV-1/efeitos dos fármacos
Precursores de Proteínas/antagonistas & inibidores
Valina/análogos & derivados
[Mh] Termos MeSH secundário: Aminocumarinas/síntese química
Sítios de Ligação
Carbamatos/síntese química
Células HEK293
Protease de HIV/metabolismo
Inibidores da Protease de HIV/síntese química
HIV-1/fisiologia
HIV-1/efeitos da radiação
Seres Humanos
Cinética
Luz
Modelos Moleculares
Fotólise
Ligação Proteica
Precursores de Proteínas/química
Precursores de Proteínas/metabolismo
Proteólise/efeitos dos fármacos
Fatores de Tempo
Valina/síntese química
Valina/farmacologia
Replicação Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Aminocoumarins); 0 (Carbamates); 0 (HIV Protease Inhibitors); 0 (Protein Precursors); 0 (p55 gag precursor protein, Human immunodeficiency virus 1); 0 (thiazol-5-ylmethyl (5-(2-amino-3-methylbutanamido)-3-hydroxy-1,6-diphenylhexan-2-yl)carbamate); EC 3.4.23.- (HIV Protease); HG18B9YRS7 (Valine)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150310
[St] Status:MEDLINE
[do] DOI:10.1038/ncomms7461


  9 / 241 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:24902899
[Au] Autor:Cook WD; Moujalled DM; Ralph TJ; Lock P; Young SN; Murphy JM; Vaux DL
[Ad] Endereço:La Trobe Institute for Molecular Science, La Trobe University, Kingsbury Drive, Bundoora, Victoria 3086, Australia.
[Ti] Título:RIPK1- and RIPK3-induced cell death mode is determined by target availability.
[So] Source:Cell Death Differ;21(10):1600-12, 2014 Oct.
[Is] ISSN:1476-5403
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Both receptor-interacting protein kinase 1 (RIPK1) and RIPK3 can signal cell death following death receptor ligation. To study the requirements for RIPK-triggered cell death in the absence of death receptor signaling, we engineered inducible versions of RIPK1 and RIPK3 that can be activated by dimerization with the antibiotic coumermycin. In the absence of TNF or other death ligands, expression and dimerization of RIPK1 was sufficient to cause cell death by caspase- or RIPK3-dependent mechanisms. Dimerized RIPK3 induced cell death by an MLKL-dependent mechanism but, surprisingly, also induced death mediated by FADD, caspase 8 and RIPK1. Catalytically active RIPK3 kinase domains were essential for MLKL-dependent but not for caspase 8-dependent death. When RIPK1 or RIPK3 proteins were dimerized, the mode of cell death was determined by the availability of downstream molecules such as FADD, caspase 8 and MLKL. These observations imply that rather than a 'switch' operating between the two modes of cell death, the final mechanism depends on levels of the respective signaling and effector proteins.
[Mh] Termos MeSH primário: Apoptose/genética
Multimerização Proteica/genética
Proteína Serina-Treonina Quinases de Interação com Receptores/genética
Proteínas Recombinantes/metabolismo
[Mh] Termos MeSH secundário: Aminocumarinas/metabolismo
Animais
Caspase 3/metabolismo
Caspase 8/metabolismo
Linhagem Celular
Proteína de Domínio de Morte Associada a Fas/metabolismo
Camundongos
Camundongos Knockout
Proteínas Quinases/metabolismo
Estrutura Quaternária de Proteína
Estrutura Terciária de Proteína
Proteínas Recombinantes/genética
Transdução de Sinais/genética
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Aminocoumarins); 0 (Fadd protein, mouse); 0 (Fas-Associated Death Domain Protein); 0 (Recombinant Proteins); 0 (Tumor Necrosis Factor-alpha); EC 2.7.- (MLKL protein, mouse); EC 2.7.- (Protein Kinases); EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases); EC 2.7.11.1 (Ripk1 protein, mouse); EC 2.7.11.1 (Ripk3 protein, mouse); EC 3.4.22.- (Caspase 3); EC 3.4.22.- (Caspase 8); PCH9QZ1IIH (coumermycin)
[Em] Mês de entrada:1506
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140607
[St] Status:MEDLINE
[do] DOI:10.1038/cdd.2014.70


  10 / 241 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:24734910
[Au] Autor:Schröder W; Bernhardt J; Marincola G; Klein-Hitpass L; Herbig A; Krupp G; Nieselt K; Wolz C
[Ti] Título:Altering gene expression by aminocoumarins: the role of DNA supercoiling in Staphylococcus aureus.
[So] Source:BMC Genomics;15:291, 2014 Apr 16.
[Is] ISSN:1471-2164
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: It has been shown previously that aminocoumarin antibiotics such as novobiocin lead to immediate downregulation of recA expression and thereby inhibit the SOS response, mutation frequency and recombination capacity in Staphylococcus aureus. Aminocoumarins function by inhibiting the ATPase activity of DNA gyrase subunit B with a severe impact on DNA supercoiling. RESULTS: Here, we have analysed the global impact of the DNA relaxing agent novobiocin on gene expression in S. aureus. Using a novobiocin-resistant mutant, it became evident that the change in recA expression is due to gyrase inhibition. Microarray analysis and northern blot hybridisation revealed that the expression levels of a distinct set of genes were increased (e.g., recF-gyrB-gyrA, the rib operon and the ure operon) or decreased (e.g., arlRS, recA, lukA, hlgC and fnbA) by novobiocin. The two-component ArlRS system was previously found to decrease the level of supercoiling in S. aureus. Thus, downregulation of arlRS might partially compensate for the relaxing effect of novobiocin. Global analysis and gene mapping of supercoiling-sensitive genes did not provide any indication that they are clustered in the genome. Promoter fusion assays confirmed that the responsiveness of a given gene is intrinsic to the promoter region but independent of the chromosomal location. CONCLUSIONS: The results indicate that the molecular properties of a given promoter, rather than the chromosomal topology, dictate the responsiveness to changes in supercoiling in the pathogen Staphylococcus aureus.
[Mh] Termos MeSH primário: Aminocumarinas/farmacologia
Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos
Staphylococcus aureus/efeitos dos fármacos
Staphylococcus aureus/genética
[Mh] Termos MeSH secundário: Antineoplásicos/farmacologia
Proteínas de Bactérias/genética
DNA Girase/metabolismo
DNA Super-Helicoidal/efeitos dos fármacos
DNA Super-Helicoidal/genética
Perfilação da Expressão Gênica
Genoma Bacteriano
Família Multigênica
Regiões Promotoras Genéticas
Recombinases Rec A/genética
Recombinases Rec A/metabolismo
Virulência/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Aminocoumarins); 0 (Antineoplastic Agents); 0 (ArlR protein, Staphylococcus aureus); 0 (Bacterial Proteins); 0 (DNA, Superhelical); EC 2.7.7.- (Rec A Recombinases); EC 5.99.1.3 (DNA Gyrase)
[Em] Mês de entrada:1411
[Cu] Atualização por classe:150806
[Lr] Data última revisão:
150806
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140417
[St] Status:MEDLINE
[do] DOI:10.1186/1471-2164-15-291



página 1 de 25 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde