Base de dados : MEDLINE
Pesquisa : D12.125.070.577 [Categoria DeCS]
Referências encontradas : 4960 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 496 ir para página                         

  1 / 4960 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27778166
[Au] Autor:Fan R; Yuan Y; Zhang Q; Zhou XR; Jia L; Liu Z; Yu C; Luo SZ; Chen L
[Ad] Endereço:Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, People's Republic of China.
[Ti] Título:Isoleucine/leucine residues at "a" and "d" positions of a heptad repeat sequence are crucial for the cytolytic activity of a short anticancer lytic peptide.
[So] Source:Amino Acids;49(1):193-202, 2017 01.
[Is] ISSN:1438-2199
[Cp] País de publicação:Austria
[La] Idioma:eng
[Ab] Resumo:Many lytic peptides contain a heptad sequence with leucine or isoleucine residues at "a" and "d" positions. However, their roles in the peptide-induced cytolytic process remain unclear. We have recently reported an anticancer lytic peptide ZXR-2 (FKIGGFIKKLWRSLLA), which contains a shortened zipper-like sequence with Ile/Leu at "a" and "d" positions. To understand the roles of these Ile/Leu residues, a series of analogs were constructed by sequentially replacing the Ile or Leu residue with alanine (Ala). Significant reduction of the cytolytic activity was observed when the Ile (3rd and 7th) and Leu (10th and 14th) residues at the "a" and "d" positions were substituted, while the replacement of the separate Leu (15th) residue had less effect. Based on the quenching of the intrinsic fluorescence of the peptides and their induced surface pressure changes of lipid monolayer, it was conjectured that the peptide ZXR-2 might insert into cell membranes from the C-terminal and to a depth of the W position. Accordingly, I , I , and L residues which mainly exposed in aqueous solution were more responsible for the peptide self-association on cell membranes, while L , together with L , might help peptide insert and anchor to cell membranes. These results are significant to elucidate the crucial roles of such Ile/Leu residues at "a" and "d" positions in peptide-peptide and peptide-membrane interactions to exert the membrane disruption activity of lytic peptides. With further understanding about the structure-activity relationship of lytic peptides, it would be helpful for designing novel anticancer lytic peptides.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Isoleucina/química
Leucina/química
Peptídeos/farmacologia
[Mh] Termos MeSH secundário: 1,2-Dipalmitoilfosfatidilcolina/análogos & derivados
1,2-Dipalmitoilfosfatidilcolina/química
Alanina/química
Sequência de Aminoácidos
Substituição de Aminoácidos
Antineoplásicos/síntese química
Linhagem Celular Tumoral
Membrana Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Colesterol/química
Células HEK293
Células HeLa
Seres Humanos
L-Lactato Desidrogenase/secreção
Lipossomos/química
Peptídeos/síntese química
Fosfatidilserinas/química
Engenharia de Proteínas
Estrutura Secundária de Proteína
Eletricidade Estática
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Liposomes); 0 (Peptides); 0 (Phosphatidylserines); 04Y7590D77 (Isoleucine); 2644-64-6 (1,2-Dipalmitoylphosphatidylcholine); 3036-82-6 (dipalmitoylphosphatidylserine); 319X2NFW0A (colfosceril palmitate); 97C5T2UQ7J (Cholesterol); EC 1.1.1.27 (L-Lactate Dehydrogenase); GMW67QNF9C (Leucine); OF5P57N2ZX (Alanine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1007/s00726-016-2350-9


  2 / 4960 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28926628
[Au] Autor:Birech Z; Mwangi PW; Bukachi F; Mandela KM
[Ad] Endereço:Department of Physics, University of Nairobi, P.O Box 30197-00100, Nairobi, Kenya.
[Ti] Título:Application of Raman spectroscopy in type 2 diabetes screening in blood using leucine and isoleucine amino-acids as biomarkers and in comparative anti-diabetic drugs efficacy studies.
[So] Source:PLoS One;12(9):e0185130, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Diabetes is an irreversible condition characterized by elevated blood glucose levels. Currently, there are no predictive biomarkers for this disease and the existing ones such as hemoglobin A1c and fasting blood glucose are used only when diabetes symptoms are noticed. The objective of this work was first to explore the potential of leucine and isoleucine amino acids as diabetes type 2 biomarkers using their Raman spectroscopic signatures. Secondly, we wanted to explore whether Raman spectroscopy can be applied in comparative efficacy studies between commercially available anti-diabetic drug pioglitazone and the locally used anti-diabetic herbal extract Momordica spinosa (Gilg.)Chiov. Sprague Dawley (SD) rat's blood was used and were pipetted onto Raman substrates prepared from conductive silver paste smeared glass slides. Prominent Raman bands associated with glucose (926, 1302, 1125 cm-1), leucine (1106, 1248, 1302, 1395 cm-1) and isolecucine (1108, 1248, 1437 and 1585 cm-1) were observed. The Raman bands centered at 1125 cm-1, 1395 cm-1 and 1437 cm-1 associated respectively to glucose, leucine and isoleucine were chosen as biomarker Raman peaks for diabetes type 2. These Raman bands displayed decreased intensities in blood from diabetic SD rats administered antidiabetic drugs pioglitazone and herbal extract Momordica spinosa (Gilg.)Chiov. The intensity decrease indicated reduced concentration levels of the respective biomarker molecules: glucose (1125 cm-1), leucine (1395 cm-1) and isoleucine (1437 cm-1) in blood. The results displayed the power and potential of Raman spectroscopy in rapid (10 seconds) diabetes and pre-diabetes screening in blood (human or rat's) with not only glucose acting as a biomarker but also leucine and isoleucine amino-acids where intensities of respectively assigned bands act as references. It also showed that using Raman spectroscopic signatures of the chosen biomarkers, the method can be an alternative for performing comparative efficacy studies between known and new anti-diabetic drugs. Reports on use of Raman spectroscopy in type 2 diabetes mellitus screening with Raman bands associated with leucine and isoleucine molecules acting as reference is rare in literature. The use of Raman spectroscopy in pre-diabetes screening of blood for changes in levels of leucine and isoleucine amino acids is particularly interesting as once elevated levels are noticed, necessary interventions to prevent diabetes development can be initiated.
[Mh] Termos MeSH primário: Diabetes Mellitus Tipo 2/diagnóstico
Isoleucina/sangue
Leucina/sangue
Análise Espectral Raman
[Mh] Termos MeSH secundário: Animais
Biomarcadores/sangue
Glicemia/análise
Diabetes Mellitus Tipo 2/tratamento farmacológico
Diabetes Mellitus Tipo 2/veterinária
Hipoglicemiantes/química
Hipoglicemiantes/uso terapêutico
Isoleucina/química
Leucina/química
Momordica/química
Momordica/metabolismo
Extratos Vegetais/química
Extratos Vegetais/uso terapêutico
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Blood Glucose); 0 (Hypoglycemic Agents); 0 (Plant Extracts); 04Y7590D77 (Isoleucine); GMW67QNF9C (Leucine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185130


  3 / 4960 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28915252
[Au] Autor:Jando J; Camargo SMR; Herzog B; Verrey F
[Ad] Endereço:Institute of Physiology, Zurich Center of Integrative Human Physiology and NCCR Kidney.CH, University of Zurich, Zurich, Switzerland.
[Ti] Título:Expression and regulation of the neutral amino acid transporter B0AT1 in rat small intestine.
[So] Source:PLoS One;12(9):e0184845, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Absorption of neutral amino acids across the luminal membrane of intestinal enterocytes is mediated by the broad neutral amino acid transporter B0AT1 (SLC6A19). Its intestinal expression depends on co-expression of the membrane-anchored peptidase angiotensin converting enzyme 2 (ACE2) and is additionally enhanced by aminopeptidase N (CD13). We investigated in this study the expression of B0AT1 and its auxiliary peptidases as well as its transport function along the rat small intestine. Additionally, we tested its possible short- and long-term regulation by dietary proteins and amino acids. We showed by immunofluorescence that B0AT1, ACE2 and CD13 co-localize on the luminal membrane of small intestinal villi and by Western blotting that their protein expression increases in distal direction. Furthermore, we observed an elevated transport activity of the neutral amino acid L-isoleucine during the nocturnal active phase compared to the inactive one. Gastric emptying was delayed by intragastric application of an amino acid cocktail but we observed no acute dietary regulation of B0AT1 protein expression and L-isoleucine transport. Investigation of the chronic dietary regulation of B0AT1, ACE2 and CD13 by different diets revealed an increased B0AT1 protein expression under amino acid-supplemented diet in the proximal section but not in the distal one and for ACE2 protein expression a reverse localization of the effect. Dietary regulation for CD13 protein expression was not as distinct as for the two other proteins. Ring uptake experiments showed a tendency for increased L-isoleucine uptake under amino acid-supplemented diet and in vivo L-isoleucine absorption was more efficient under high protein and amino acid-supplemented diet. Additionally, plasma levels of branched-chain amino acids were elevated under high protein and amino acid diet. Taken together, our experiments did not reveal an acute amino acid-induced regulation of B0AT1 but revealed a chronic dietary adaptation mainly restricted to the proximal segment of the small intestine.
[Mh] Termos MeSH primário: Sistemas de Transporte de Aminoácidos Neutros/biossíntese
Antígenos CD13/metabolismo
Regulação da Expressão Gênica/efeitos dos fármacos
Intestino Delgado/metabolismo
Isoleucina/farmacologia
Peptidil Dipeptidase A/metabolismo
[Mh] Termos MeSH secundário: Animais
Suplementos Nutricionais
Masculino
Ratos
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acid Transport Systems, Neutral); 0 (SLC6A19 protein, rat); 04Y7590D77 (Isoleucine); EC 3.4.11.2 (CD13 Antigens); EC 3.4.15.1 (Peptidyl-Dipeptidase A); EC 3.4.17.- (angiotensin converting enzyme 2)
[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:170916
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184845


  4 / 4960 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28876052
[Au] Autor:Spencer RK; Hochbaum AI
[Ad] Endereço:Department of Chemistry and Department of Chemical Engineering & Materials Science, University of California, Irvine , Irvine, California 92697-2575, United States.
[Ti] Título:The Phe-Ile Zipper: A Specific Interaction Motif Drives Antiparallel Coiled-Coil Hexamer Formation.
[So] Source:Biochemistry;56(40):5300-5308, 2017 Oct 10.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Coiled coils are a robust motif for exploring amino acid interactions, generating unique supramolecular structures, and expanding the functional properties of biological materials. A recently discovered antiparallel coiled-coil hexamer (ACC-Hex, peptide 1) exhibits a unique interaction in which Phe and Ile residues from adjacent α-helices interact to form a Phe-Ile zipper within the hydrophobic core. Analysis of the X-ray crystallographic structure of ACC-Hex suggests that the stability of the six-helix bundle relies on specific interactions between the Phe and Ile residues. The Phe-Ile zipper is unprecedented and represents a powerful tool for utilizing the Phe-Ile interactions to direct supramolecular assembly. To further probe and understand the limits of the Phe-Ile zipper, we designed peptide sequences with natural and unnatural amino acids placed at the Phe and Ile residue positions. Using size exclusion chromatography and small-angle X-ray scattering, we found that the proper assembly of ACC-Hex from monomers is sensitive to subtle changes in side chain steric bulk and hydrophobicity introduced by mutations at the Phe and Ile residue positions. Of the sequence variants that formed ACC-Hex, mutations in the hydrophobic core significantly affected the stability of the hexamer, from a ΔG of 2-8 kcal mol . Additional sequences were designed to further probe and enhance the stability of the ACC-Hex system by maximizing salt bridging between the solvent-exposed residues. Finally, we expanded on the generality of the Phe-Ile zipper, creating a unique sequence that forms an antiparallel hexamer that is topologically similar to ACC-Hex but atomistically unique.
[Mh] Termos MeSH primário: Isoleucina
Peptídeos/química
Peptídeos/metabolismo
Fenilalanina
Multimerização Proteica
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Modelos Moleculares
Mutação
Peptídeos/genética
Conformação Proteica em alfa-Hélice
Estabilidade Proteica
Solventes/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Peptides); 0 (Solvents); 04Y7590D77 (Isoleucine); 47E5O17Y3R (Phenylalanine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170907
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00756


  5 / 4960 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28851624
[Au] Autor:Khan SH; Islam A; Hassan MI; Sharma S; Singh TP; Ahmad F
[Ad] Endereço:Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.
[Ti] Título:Effect of conservative mutations (L94V and L94I) on the structure and stability of horse cytochrome c.
[So] Source:Arch Biochem Biophys;633:40-49, 2017 Nov 01.
[Is] ISSN:1096-0384
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A sequence alignment of horse cytochrome c (cyt c) with all known cyts c shows that Leu at position 94 is conserved, except in 14 species which have either Val or Ile at this position. It is also known that Leu94 of the mammalian cyt c plays an important role in folding and stability. The important question here is as to what will happen in terms of folding and stability if Leu94 of the mammalian cyt c is substituted by Val or Ile. To answer this question, we introduced natural substitutes of Leu94 by Val and Ile in horse cyt c. The purified L94V and L94I mutants under native condition (pH 6.0, 25 °C) were characterized using far-UV, near-UV and Soret- circular dichroism, visible absorbance, Trp and ANS (1-anilino-8-napthaline sulphonate) fluorescence and dynamic light scattering measurements. Furthermore, stability parameters T (mid-point of denaturation) and ΔG (Gibbs free energy change at 25 °C) were also determined using spectroscopic and differential scanning calorimetric methods. All these measurements led us to conclude that both mutants exist as molten globule and are less stable than the wild-type protein. These observations are supported well by examining the structure of horse cyt c (PDB ID, 1HRC).
[Mh] Termos MeSH primário: Citocromos c/química
Isoleucina/química
Leucina/química
Mutação
Valina/química
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Substituição de Aminoácidos
Animais
Sítios de Ligação
Clonagem Molecular
Citocromos c/genética
Citocromos c/metabolismo
Estabilidade Enzimática
Escherichia coli/genética
Escherichia coli/metabolismo
Expressão Gênica
Cavalos
Isoleucina/metabolismo
Cinética
Leucina/metabolismo
Ligação Proteica
Domínios e Motivos de Interação entre Proteínas
Estrutura Secundária de Proteína
Estrutura Terciária de Proteína
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Especificidade por Substrato
Termodinâmica
Valina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Recombinant Proteins); 04Y7590D77 (Isoleucine); 9007-43-6 (Cytochromes c); GMW67QNF9C (Leucine); HG18B9YRS7 (Valine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170831
[St] Status:MEDLINE


  6 / 4960 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28731268
[Au] Autor:Zhang M; Yu XW; Xu Y; Jouhten P; Swapna GVT; Glaser RW; Hunt JF; Montelione GT; Maaheimo H; Szyperski T
[Ad] Endereço:School of Biotechnology, Key Laboratory of Industrial Biotechnology, State Key Laboratory of Food Science and Technology, Ministry of Education, Jiangnan University, Wuxi, China.
[Ti] Título: C metabolic flux profiling of Pichia pastoris grown in aerobic batch cultures on glucose revealed high relative anabolic use of TCA cycle and limited incorporation of provided precursors of branched-chain amino acids.
[So] Source:FEBS J;284(18):3100-3113, 2017 Sep.
[Is] ISSN:1742-4658
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Carbon metabolism of Crabtree-negative yeast Pichia pastoris was profiled using C nuclear magnetic resonance (NMR) to delineate regulation during exponential growth and to study the import of two precursors for branched-chain amino acid biosynthesis, α-ketoisovalerate and α-ketobutyrate. Cells were grown in aerobic batch cultures containing (a) only glucose, (b) glucose along with the precursors, or (c) glucose and Val. The study provided the following new insights. First, C flux ratio analyses of central metabolism reveal an unexpectedly high anaplerotic supply of the tricarboxylic acid cycle for a Crabtree-negative yeast, and show that a substantial fraction of glucose catabolism proceeds through the pentose phosphate pathway. A comparison with previous flux ratio analyses for batch cultures of Crabtree-negative Pichia stipitis and Crabtree-positive Saccharomyces cerevisiae indicate that the overall regulation of central carbon metabolism in P. pastoris is intermediate in between P. stipitis and S. cerevisiae. Second, excess α-ketoisovalerate in the medium is not transported into the cytoplasm indicating that P. pastoris lacks a suitable transporter. In contrast, excess Val is efficiently taken up and largely fulfills demands for both Val and Leu for protein synthesis. Third, excess α-ketobutyrate is transported into the mitochondria for Ile biosynthesis. However, the import does not efficiently inhibit the synthesis of α-ketobutyrate from pyruvate indicating that P. pastoris has not been optimized evolutionarily to take full advantage of this carbon source. These findings have direct implications for preparing uniformly H, C, N-labeled proteins containing protonated Ile, Val, and Leu methyl groups in P. pastoris for NMR-based structural biology. ENZYMES: Acetohydroxy acid isomeroreductase (EC 1.1.1.86), branched-chain amino acid aminotransferase (BCAT, EC 2.6.1.42), fumarase (EC 4.2.1.2), malic enzyme (EC 1.1.1.39/1.1.1.40), phosphoenolpyruvate carboxykinase (EC 4.1.1.49), pyruvate carboxylase (EC 6.4.1.1), pyruvate kinase (EC 2.7.1.40), l-serine hydroxymethyltransferase (EC 2.1.2.1), threonine aldolase (EC 4.1.2.5), threonine dehydratase (EC 4.3.1.19); transketolase (EC 2.2.1.1), transaldolase (EC 2.2.1.2).
[Mh] Termos MeSH primário: Glucose/metabolismo
Isoleucina/metabolismo
Leucina/metabolismo
Metaboloma/fisiologia
Pichia/metabolismo
Valina/metabolismo
[Mh] Termos MeSH secundário: Aerobiose/fisiologia
Técnicas de Cultura Celular por Lotes
Butiratos/metabolismo
Isótopos de Carbono
Ciclo do Ácido Cítrico/fisiologia
Cetoácidos/metabolismo
Espectroscopia de Ressonância Magnética
Mitocôndrias/metabolismo
Via de Pentose Fosfato/fisiologia
Ácido Pirúvico/metabolismo
Saccharomyces cerevisiae/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Butyrates); 0 (Carbon Isotopes); 0 (Keto Acids); 04Y7590D77 (Isoleucine); 600-18-0 (alpha-ketobutyric acid); 759-05-7 (alpha-ketoisovalerate); 8558G7RUTR (Pyruvic Acid); GMW67QNF9C (Leucine); HG18B9YRS7 (Valine); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171004
[Lr] Data última revisão:
171004
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170722
[St] Status:MEDLINE
[do] DOI:10.1111/febs.14180


  7 / 4960 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28605514
[Au] Autor:Shi D; Svetlov D; Abagyan R; Artsimovitch I
[Ad] Endereço:Department of Chemistry and Biochemistry, University of California, San Diego, CA 92093, USA.
[Ti] Título:Flipping states: a few key residues decide the winning conformation of the only universally conserved transcription factor.
[So] Source:Nucleic Acids Res;45(15):8835-8843, 2017 Sep 06.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Transcription factors from the NusG family bind to the elongating RNA polymerase to enable synthesis of long RNAs in all domains of life. In bacteria, NusG frequently co-exists with specialized paralogs that regulate expression of a small set of targets, many of which encode virulence factors. Escherichia coli RfaH is the exemplar of this regulatory mechanism. In contrast to NusG, which freely binds to RNA polymerase, RfaH exists in a structurally distinct autoinhibitory state in which the RNA polymerase-binding site is buried at the interface between two RfaH domains. Binding to an ops DNA sequence triggers structural transformation wherein the domains dissociate and RfaH refolds into a NusG-like structure. Formation of the autoinhibitory state, and thus sequence-specific recruitment, represents the decisive step in the evolutionary history of the RfaH subfamily. We used computational and experimental approaches to identify the residues that confer the unique regulatory properties of RfaH. Our analysis highlighted highly conserved Ile and Phe residues at the RfaH interdomain interface. Replacement of these residues with equally conserved Glu and Val counterpart residues in NusG destabilized interactions between the RfaH domains and allowed sequence-independent recruitment to RNA polymerase, suggesting a plausible pathway for diversification of NusG paralogs.
[Mh] Termos MeSH primário: DNA Bacteriano/química
RNA Polimerases Dirigidas por DNA/química
Proteínas de Escherichia coli/química
Regulação Bacteriana da Expressão Gênica
Fatores de Alongamento de Peptídeos/química
Transativadores/química
Fatores de Transcrição/química
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Substituição de Aminoácidos
Sítios de Ligação
DNA Bacteriano/genética
DNA Bacteriano/metabolismo
RNA Polimerases Dirigidas por DNA/genética
RNA Polimerases Dirigidas por DNA/metabolismo
Escherichia coli/genética
Escherichia coli/metabolismo
Proteínas de Escherichia coli/genética
Proteínas de Escherichia coli/metabolismo
Evolução Molecular
Ácido Glutâmico/química
Ácido Glutâmico/metabolismo
Isoleucina/química
Isoleucina/metabolismo
Modelos Moleculares
Fatores de Alongamento de Peptídeos/genética
Fatores de Alongamento de Peptídeos/metabolismo
Fenilalanina/química
Fenilalanina/metabolismo
Ligação Proteica
Dobramento de Proteína
Domínios e Motivos de Interação entre Proteínas
Alinhamento de Sequência
Homologia de Sequência de Aminoácidos
Transativadores/genética
Transativadores/metabolismo
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
Transcrição Genética
Valina/química
Valina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Bacterial); 0 (Escherichia coli Proteins); 0 (NusG protein, E coli); 0 (Peptide Elongation Factors); 0 (RfaH protein, E coli); 0 (Trans-Activators); 0 (Transcription Factors); 04Y7590D77 (Isoleucine); 3KX376GY7L (Glutamic Acid); 47E5O17Y3R (Phenylalanine); EC 2.7.7.6 (DNA-Directed RNA Polymerases); HG18B9YRS7 (Valine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170613
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx523


  8 / 4960 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28584051
[Au] Autor:Mowrey DD; Xu L; Mei Y; Pasek DA; Meissner G; Dokholyan NV
[Ad] Endereço:From the Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7260.
[Ti] Título:Ion-pulling simulations provide insights into the mechanisms of channel opening of the skeletal muscle ryanodine receptor.
[So] Source:J Biol Chem;292(31):12947-12958, 2017 Aug 04.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The type 1 ryanodine receptor (RyR1) mediates Ca release from the sarcoplasmic reticulum to initiate skeletal muscle contraction and is associated with muscle diseases, malignant hyperthermia, and central core disease. To better understand RyR1 channel function, we investigated the molecular mechanisms of channel gating and ion permeation. An adequate model of channel gating requires accurate, high-resolution models of both open and closed states of the channel. To this end, we generated an open-channel RyR1 model using molecular simulations to pull Ca through the pore constriction site of a closed-channel RyR1 structure determined at 3.8-Šresolution. Importantly, we find that our open-channel model is consistent with the RyR1 and cardiac RyR (RyR2) open-channel structures reported while this paper was in preparation. Both our model and the published structures show similar rotation of the upper portion of the pore-lining S6 helix away from the 4-fold channel axis and twisting of Ile-4937 at the channel constriction site out of the channel pore. These motions result in a minimum open-channel pore radius of ∼3 Šformed by Gln-4933, rather than Ile-4937 in the closed-channel structure. We also present functional support for our model by mutations around the closed- and open-channel constriction sites (Gln-4933 and Ile-4937). Our results indicate that use of ion-pulling simulations produces a RyR1 open-channel model, which can provide insights into the mechanisms of channel opening complementing those from the structural data.
[Mh] Termos MeSH primário: Sinalização do Cálcio
Bicamadas Lipídicas/química
Modelos Moleculares
Canal de Liberação de Cálcio do Receptor de Rianodina/química
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Animais
Cafeína/química
Cafeína/metabolismo
Cafeína/farmacologia
Agonistas dos Canais de Cálcio/química
Agonistas dos Canais de Cálcio/metabolismo
Agonistas dos Canais de Cálcio/farmacologia
Sinalização do Cálcio/efeitos dos fármacos
Glutamina/química
Células HEK293
Seres Humanos
Isoleucina/química
Ligantes
Simulação de Dinâmica Molecular
Mutação
Fragmentos de Peptídeos/agonistas
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Conformação Proteica em alfa-Hélice
Domínios e Motivos de Interação entre Proteínas
Coelhos
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Rianodina/química
Rianodina/metabolismo
Rianodina/farmacologia
Canal de Liberação de Cálcio do Receptor de Rianodina/genética
Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channel Agonists); 0 (Ligands); 0 (Lipid Bilayers); 0 (Peptide Fragments); 0 (Recombinant Proteins); 0 (Ryanodine Receptor Calcium Release Channel); 04Y7590D77 (Isoleucine); 0RH81L854J (Glutamine); 15662-33-6 (Ryanodine); 3G6A5W338E (Caffeine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170825
[Lr] Data última revisão:
170825
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170607
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.760199


  9 / 4960 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28575390
[Au] Autor:Ji QQ; Fang ZP; Ye Q; Chi CW; Wang ED
[Ad] Endereço:State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences; University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, P. R. China.
[Ti] Título:Self-protective responses to norvaline-induced stress in a leucyl-tRNA synthetase editing-deficient yeast strain.
[So] Source:Nucleic Acids Res;45(12):7367-7381, 2017 Jul 07.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The editing function of aminoacyl-tRNA synthetases (aaRSs) is indispensible for formation of the correct aminoacyl-tRNAs. Editing deficiency may lead to growth inhibition and the pathogenesis of various diseases. Herein, we confirmed that norvaline (Nva) but not isoleucine or valine is the major threat to the editing function of Saccharomyces cerevisiae leucyl-tRNA synthetase (ScLeuRS), both in vitro and in vivo. Nva could be misincorporated into the proteome of the LeuRS editing-deficient yeast strain (D419A/ScΔleuS), potentially resulting in dysfunctional protein folding and growth delay. Furthermore, the exploration of the Nva-induced intracellular stress response mechanism in D419A/ScΔleuS revealed that Hsp70 chaperones were markedly upregulated in response to the potential protein misfolding. Additionally, proline (Pro), glutamate (Glu) and glutamine (Gln), which may accumulate due to the conversion of Nva, collectively contributed to the reduction of reactive oxygen species (ROS) levels in Nva-treated D419A/ScΔleuS cells. In conclusion, our study highlights the significance of the editing function of LeuRS and provides clues for understanding the intracellular stress protective mechanisms that are triggered in aaRS editing-deficient organisms.
[Mh] Termos MeSH primário: Regulação Fúngica da Expressão Gênica
Leucina-tRNA Ligase/genética
Edição de RNA
Proteínas de Saccharomyces cerevisiae/genética
Saccharomyces cerevisiae/efeitos dos fármacos
Valina/análogos & derivados
[Mh] Termos MeSH secundário: Ácido Glutâmico/metabolismo
Ácido Glutâmico/farmacologia
Glutamina/metabolismo
Glutamina/farmacologia
Proteínas de Choque Térmico HSP70/genética
Proteínas de Choque Térmico HSP70/metabolismo
Isoleucina/metabolismo
Isoleucina/farmacologia
Cinética
Leucina-tRNA Ligase/metabolismo
Prolina/metabolismo
Prolina/farmacologia
Dobramento de Proteína
Espécies Reativas de Oxigênio/metabolismo
Saccharomyces cerevisiae/enzimologia
Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/metabolismo
Estresse Fisiológico
Valina/metabolismo
Valina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HSP70 Heat-Shock Proteins); 0 (Reactive Oxygen Species); 0 (Saccharomyces cerevisiae Proteins); 04Y7590D77 (Isoleucine); 0RH81L854J (Glutamine); 3KX376GY7L (Glutamic Acid); 9DLQ4CIU6V (Proline); A70UKS48FE (norvaline); EC 6.1.1.4 (Leucine-tRNA Ligase); HG18B9YRS7 (Valine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170603
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx487


  10 / 4960 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28552956
[Au] Autor:Zwingerman N; Medina-Rivera A; Kassam I; Wilson MD; Morange PE; Trégouët DA; Gagnon F
[Ad] Endereço:Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
[Ti] Título:Sex-specific effect of CPB2 Ala147Thr but not Thr325Ile variants on the risk of venous thrombosis: A comprehensive meta-analysis.
[So] Source:PLoS One;12(5):e0177768, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Thrombin activatable fibrinolysis inhibitor (TAFI), encoded by the Carboxypeptidase B2 gene (CPB2), is an inhibitor of fibrinolysis and plays a role in the pathogenesis of venous thrombosis. Experimental findings support a functional role of genetic variants in CPB2, while epidemiological studies have been unable to confirm associations with risk of venous thrombosis. Sex-specific effects could underlie the observed inconsistent associations between CPB2 genetic variants and venous thrombosis. METHODS: A comprehensive literature search was conducted for associations between Ala147Thr and Thr325Ile variants with venous thrombosis. Authors were contacted to provide sex-specific genotype counts from their studies. Combined and sex-specific random effects meta-analyses were used to estimate a pooled effect estimate for primary and secondary genetic models. RESULTS: A total of 17 studies met the inclusion criteria. A sex-specific meta-analysis applying a dominant model supported a protective effect of Ala147Thr on venous thrombosis in females (OR = 0.81, 95%CI: 0.68,0.97; p = 0.018), but not in males (OR = 1.06, 95%CI:0.96-1.16; p = 0.263). The Thr325Ile did not show a sex-specific effect but showed variation in allele frequencies by geographic region. A subgroup analysis of studies in European countries showed decreased risk, with a recessive model (OR = 0.83, 95%CI:0.71-0.97, p = 0.021) for venous thrombosis. CONCLUSIONS: A comprehensive literature review, including unpublished data, provided greater statistical power for the analyses and decreased the likelihood of publication bias influencing the results. Sex-specific analyses explained apparent discrepancies across genetic studies of Ala147Thr and venous thrombosis. While, careful selection of genetic models based on population genetics, evolutionary and biological knowledge can increase power by decreasing the need to adjust for testing multiple models.
[Mh] Termos MeSH primário: Alanina/genética
Carboxipeptidase B2/genética
Predisposição Genética para Doença
Fatores Sexuais
Treonina/genética
Trombose Venosa/genética
[Mh] Termos MeSH secundário: Feminino
Seres Humanos
Isoleucina/genética
Masculino
Fatores de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS
[Nm] Nome de substância:
04Y7590D77 (Isoleucine); 2ZD004190S (Threonine); EC 3.4.17.20 (CPB2 protein, human); EC 3.4.17.20 (Carboxypeptidase B2); OF5P57N2ZX (Alanine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170921
[Lr] Data última revisão:
170921
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170530
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0177768



página 1 de 496 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