Base de dados : MEDLINE
Pesquisa : D08.811.520.232.400.600 [Categoria DeCS]
Referências encontradas : 588 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 59 ir para página                         

  1 / 588 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28461448
[Au] Autor:Borchert AJ; Downs DM
[Ad] Endereço:Department of Microbiology, University of Georgia, Athens, Georgia, USA.
[Ti] Título:The Response to 2-Aminoacrylate Differs in Escherichia coli and Salmonella enterica, despite Shared Metabolic Components.
[So] Source:J Bacteriol;199(14), 2017 07 15.
[Is] ISSN:1098-5530
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The metabolic network of an organism includes the sum total of the biochemical reactions present. In microbes, this network has an impeccable ability to sense and respond to perturbations caused by internal or external stimuli. The metabolic potential (i.e., network structure) of an organism is often drawn from the genome sequence, based on the presence of enzymes deemed to indicate specific pathways. and are members of the family of Gram-negative bacteria that share the majority of their metabolic components and regulatory machinery as the "core genome." In , the ability of the enamine intermediate 2-aminoacrylate (2AA) to inactivate a number of pyridoxal 5'-phosphate (PLP)-dependent enzymes has been established In this study, 2AA metabolism and the consequences of its accumulation were investigated in The data showed that despite the conservation of all relevant enzymes, and differed in both the generation and detrimental consequences of 2AA. In total, these findings suggest that the structure of the metabolic network surrounding the generation and response to endogenous 2AA stress differs between and This work compared the metabolic networks surrounding the endogenous stressor 2-aminoacrylate in two closely related members of the The data showed that despite the conservation of all relevant enzymes in this metabolic node, the two closely related organisms diverged in their metabolic network structures. This work highlights how a set of conserved components can generate distinct network architectures and how this can impact the physiology of an organism. This work defines a model to expand our understanding of the 2-aminoacrylate stress response and the differences in metabolic structures and cellular milieus between and .
[Mh] Termos MeSH primário: Acrilatos/farmacologia
Proteínas de Bactérias/metabolismo
Escherichia coli/efeitos dos fármacos
Salmonella enterica/efeitos dos fármacos
[Mh] Termos MeSH secundário: Adenina/farmacologia
Ácido Aspártico/farmacologia
Proteínas de Bactérias/genética
Escherichia coli/metabolismo
Deleção de Genes
Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos
Regulação Enzimológica da Expressão Gênica/fisiologia
L-Serina Desidratase/genética
L-Serina Desidratase/metabolismo
Salmonella enterica/metabolismo
Estresse Fisiológico/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Acrylates); 0 (Bacterial Proteins); 30KYC7MIAI (Aspartic Acid); EC 4.3.1.17 (L-Serine Dehydratase); JAC85A2161 (Adenine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  2 / 588 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27585868
[Au] Autor:Talukdar G; Inoue R; Yoshida T; Ishimoto T; Yaku K; Nakagawa T; Mori H
[Ad] Endereço:Department of Molecular Neuroscience, Graduate School of Innovative Life Science and Medicine and Pharmaceutical Sciences, University of Toyama, Japan; Department of Biochemistry, TMSS Medical College & Hospital, Bangladesh.
[Ti] Título:Novel role of serine racemase in anti-apoptosis and metabolism.
[So] Source:Biochim Biophys Acta;1861(1 Pt A):3378-3387, 2017 01.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Serine racemase (SR) catalyzes the production of d-serine, a co-agonist of the N-methyl-d-aspartate receptor (NMDAR). A previous report shows the contribution of SR in the NMDAR-mediated neuronal cell death process. METHODS AND RESULTS: To analyze the intrinsic role of SR in the cell death process, we established the epithelial human embryonic kidney 293T (HEK293T) cell lines expressing wild-type SR (SR-WT), catalytically inactive mutant SR (SR-K56G), and catalytically hyperactive mutant SR (SR-Q155D). To these cell lines, staurosporine (STS), which induces apoptosis, was introduced. The cells expressing SR-WT and SR-Q155D showed resistance to STS-induced apoptosis, compared with nontransfected HEK293T cells and cells expressing SR-K56G. The SR-WT cells also showed a significant higher viability than the SR-QD cells. Furthermore, we detected elevated phosphorylation levels of Bcl-2 at serine-70 and Akt at serine-473 and threonine-308, which are related to cell survival, in the cells expressing SR-WT and SR-Q155D. From the results of metabolite analysis, we found elevated levels of acetyl CoA and ATP in cells expressing SR-WT. CONCLUSION: Because SR has two enzymatic activities, namely, racemization and α, ß-elimination, and SR-Q155D shows enhanced racemization and reduced α, ß-elimination activities, we concluded that the racemization reaction catalyzed by SR may have a more protective role against apoptosis than the α, ß-elimination reaction. Moreover, both of these activities are important for maximal survival and elevated levels of acetyl CoA and ATP. GENERAL SIGNIFICANCE: Our findings reveal the NMDAR-independent roles of SR in metabolism and cell survival.
[Mh] Termos MeSH primário: Apoptose
Metabolismo
Racemases e Epimerases/metabolismo
[Mh] Termos MeSH secundário: Animais
Caspase 3/metabolismo
Citocromos c/metabolismo
Glicólise/efeitos dos fármacos
Células HEK293
Seres Humanos
L-Serina Desidratase/metabolismo
Metabolômica
Camundongos
Mitocôndrias/efeitos dos fármacos
Mitocôndrias/metabolismo
Modelos Biológicos
Fosforilação/efeitos dos fármacos
Complexo Piruvato Desidrogenase/metabolismo
Estaurosporina/farmacologia
Transfecção
Proteína de Morte Celular Associada a bcl/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Pyruvate Dehydrogenase Complex); 0 (bcl-Associated Death Protein); 9007-43-6 (Cytochromes c); EC 3.4.22.- (Caspase 3); EC 4.3.1.17 (L-Serine Dehydratase); EC 5.1.- (Racemases and Epimerases); EC 5.1.1.16 (serine racemase); H88EPA0A3N (Staurosporine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171103
[Lr] Data última revisão:
171103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160903
[St] Status:MEDLINE


  3 / 588 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27072285
[Au] Autor:Pemberton TA; Christianson DW
[Ad] Endereço:Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA, USA.
[Ti] Título:General base-general acid catalysis by terpenoid cyclases.
[So] Source:J Antibiot (Tokyo);69(7):486-93, 2016 Jul.
[Is] ISSN:0021-8820
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Terpenoid cyclases catalyze the most complex reactions in biology, in that more than half of the substrate carbon atoms often undergo changes in bonding during the course of a multistep cyclization cascade that proceeds through multiple carbocation intermediates. Many cyclization mechanisms require stereospecific deprotonation and reprotonation steps, and most cyclization cascades are terminated by deprotonation to yield an olefin product. The first bacterial terpenoid cyclase to yield a crystal structure was pentalenene synthase from Streptomyces exfoliatus UC5319. This cyclase generates the hydrocarbon precursor of the pentalenolactone family of antibiotics. The structures of pentalenene synthase and other terpenoid cyclases reveal predominantly nonpolar active sites typically lacking amino acid side chains capable of serving general base-general acid functions. What chemical species, then, enables the Brønsted acid-base chemistry required in the catalytic mechanisms of these enzymes? The most likely candidate for such general base-general acid chemistry is the co-product inorganic pyrophosphate. Here, we briefly review biological and nonbiological systems in which phosphate and its derivatives serve general base and general acid functions in catalysis. These examples highlight the fact that the Brønsted acid-base activities of phosphate derivatives are comparable to the Brønsted acid-base activities of amino acid side chains.
[Mh] Termos MeSH primário: Liases Intramoleculares/química
Terpenos/metabolismo
[Mh] Termos MeSH secundário: Aspartato Carbamoiltransferase/química
Aspartato Carbamoiltransferase/metabolismo
Biocatálise
Ciclização
Difosfatos/química
Difosfatos/metabolismo
Geraniltranstransferase/química
Geraniltranstransferase/metabolismo
Hidrolases/química
Hidrolases/metabolismo
Liases Intramoleculares/metabolismo
Isomerases/química
Isomerases/metabolismo
L-Serina Desidratase/química
L-Serina Desidratase/metabolismo
Fosfatos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Diphosphates); 0 (Phosphates); 0 (Terpenes); 4E862E7GRQ (diphosphoric acid); EC 2.1.3.2 (Aspartate Carbamoyltransferase); EC 2.5.1.10 (Geranyltranstransferase); EC 3.- (Hydrolases); EC 3.7.1.3 (kynureninase); EC 4.3.1.17 (L-Serine Dehydratase); EC 5.- (Isomerases); EC 5.- (aristolochene synthase); EC 5.5.- (Intramolecular Lyases); EC 5.5.- (farnesylpyrophosphate cyclase)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170701
[Lr] Data última revisão:
170701
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160414
[St] Status:MEDLINE
[do] DOI:10.1038/ja.2016.39


  4 / 588 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26971469
[Au] Autor:Xu XL; Grant GA
[Ad] Endereço:Developmental Biology, Washington University School of Medicine, 660 S. Euclid Avenue, Box 8103, St. Louis, MO 63110, USA.
[Ti] Título:Mutagenic and chemical analyses provide new insight into enzyme activation and mechanism of the type 2 iron-sulfur l-serine dehydratase from Legionella pneumophila.
[So] Source:Arch Biochem Biophys;596:108-17, 2016 Apr 15.
[Is] ISSN:1096-0384
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The crystal structure of the Type 2 l-serine dehydratase from Legionella pneumophila (lpLSD), revealed a "tail-in-mouth" configuration where the C-terminal residue acts as an intrinsic competitive inhibitor. This pre-catalytic structure undergoes an activation step prior to catalytic turnover. Mutagenic analysis of residues at or near the active site cleft is consistent with stabilization of substrate binding by many of the same residues that interact with the C-terminal cysteine and highlight the critical role of certain tail residues in activity. pH-rate profiles show that a residue with pK of 5.9 must be deprotonated and a residue with a pK of 8.5 must be protonated for activity. This supports an earlier suggestion that His 61 is the likely catalytic base. An additional residue with a pK of 8.5-9 increases cooperativity when it is deprotonated. This investigation also demonstrates that the Fe-S dehydratases convert the enamine/imine intermediates of the catalytic reaction to products on the enzyme prior to release. This is in contrast to pyridoxyl 5' phosphate based dehydratases that release an enamine/imine intermediate into solution, which then hydrolyzes to produce the ketoamine product.
[Mh] Termos MeSH primário: Proteínas de Bactérias/química
L-Serina Desidratase/química
Legionella pneumophila/enzimologia
Mutagênese
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
Catálise
Ativação Enzimática/genética
Concentração de Íons de Hidrogênio
L-Serina Desidratase/genética
Legionella pneumophila/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); EC 4.3.1.17 (L-Serine Dehydratase)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170428
[Lr] Data última revisão:
170428
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160315
[St] Status:MEDLINE


  5 / 588 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26652711
[Au] Autor:Hoskin SO; Bremner DM; Holtrop G; Lobley GE
[Ad] Endereço:1Rowett Institute of Nutrition and Health,University of Aberdeen,Greenburn Road,Bucksburn,Aberdeen AB21 9SB,UK.
[Ti] Título:Responses in whole-body amino acid kinetics to an acute, sub-clinical endotoxin challenge in lambs.
[So] Source:Br J Nutr;115(4):576-84, 2016 Feb 28.
[Is] ISSN:1475-2662
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Some effects of parasitism, endotoxaemia or sepsis can be mitigated by provision of extra protein. Supplemented protein may encompass a metabolic requirement for specific amino acids (AA). The current study investigates a method to identify and quantify the amounts of AA required during inflammation induced by an endotoxin challenge. One of each pair of six twin sheep was infused in the jugular vein for 20 h with either saline (control) or lipopolysaccharide (LPS, 2 ng/kg body weight per min) from Escherichia coli. Between 12 and 20 h a mixture of stable isotope-labelled AA was infused to measure irreversible loss rates. From 16 to 20 h all sheep were supplemented with a mixture of unlabelled AA infused intravenously. Blood samples were taken before the start of infusions, and then continuously over intervals between 14 and 20 h. At 20 h the sheep were euthanised, and liver and kidney samples were taken for measurement of serine-threonine dehydratase (SDH) activity. LPS infusion decreased plasma concentrations of most AA (P<0·05; P<0·10 for leucine and tryptophan), except for phenylalanine (which increased P=0·022) and tyrosine. On the basis of the incremental response to the supplemental AA, arginine, aspartate, cysteine, glutamate, lysine (tendency only), glycine, methionine, proline, serine and threonine were important in the metabolic response to the endotoxaemia. The AA infusion between 16 and 20 h restored the plasma concentrations in the LPS-treated sheep for the majority of AA, except for glutamine, isoleucine, methionine, serine and valine. LPS treatment increased (P<0·02) SDH activity in both liver and kidney. The approach allows quantification of key AA required during challenge situations.
[Mh] Termos MeSH primário: Aminoácidos/metabolismo
Fenômenos Fisiológicos da Nutrição Animal
Endotoxemia/veterinária
Infecções por Escherichia coli/veterinária
Necessidades Nutricionais
Doenças dos Ovinos/metabolismo
[Mh] Termos MeSH secundário: Aminoácidos/administração & dosagem
Aminoácidos/sangue
Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos
Animais
Cruzamentos Genéticos
Relação Dose-Resposta a Droga
Endotoxemia/sangue
Endotoxemia/imunologia
Endotoxemia/metabolismo
Escherichia coli/imunologia
Infecções por Escherichia coli/sangue
Infecções por Escherichia coli/imunologia
Infecções por Escherichia coli/metabolismo
Feminino
Infusões Intravenosas
Rim/enzimologia
Rim/imunologia
Rim/metabolismo
Cinética
L-Serina Desidratase/metabolismo
Lipopolissacarídeos/administração & dosagem
Lipopolissacarídeos/toxicidade
Fígado/enzimologia
Fígado/imunologia
Fígado/metabolismo
Masculino
Análise por Pareamento
Projetos Piloto
Ovinos
Doenças dos Ovinos/sangue
Doenças dos Ovinos/imunologia
Carneiro Doméstico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amino Acids); 0 (Lipopolysaccharides); EC 4.3.1.17 (L-Serine Dehydratase)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:160130
[Lr] Data última revisão:
160130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151215
[St] Status:MEDLINE
[do] DOI:10.1017/S0007114515004894


  6 / 588 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26875484
[Au] Autor:Yoshimura R; Takai M; Namaki H; Minami K; Imamura W; Kato H; Kamei Y; Kanamoto R
[Ad] Endereço:Laboratory of Molecular Nutrition, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University.
[Ti] Título:Down Regulation of Asparagine Synthetase and 3-Phosphoglycerate Dehydrogenase, and the Up-Regulation of Serine Dehydratase in Rat Liver from Intake of Excess Amount of Leucine Are Not Related to Leucine-Caused Amino Acid Imbalance.
[So] Source:J Nutr Sci Vitaminol (Tokyo);61(6):441-8, 2015.
[Is] ISSN:1881-7742
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Asparagine synthetase (ASNS), 3-phosphoglycerate dehydrogenase (PHGDH) and serine dehydratase (SDS) in rat liver are expressed in response to protein and amino acid intake. In the present study, we examined the expression of these enzymes in relation to amino acid imbalance caused by leucine. Rats were subjected to leucine administration in the diet or orally between meals. Consumption of more than 2% leucine in a 6% casein diet suppressed food intake and caused growth retardation in a dose-dependent manner, but this was not seen in a 12% or 40% casein diet. ASNS and PHGDH expression in the liver was significantly induced by the 6% casein diet and was suppressed by leucine in a dose-dependent manner, whereas the SDS expression was induced. These effects were leucine specific and not seen with ingestion of isoleucine or valine. However, leucine orally administered between meals did not change the food intake or growth of rats fed a 6% casein die, though it similarly affected the expression of ASNS, PHGDH and SDS in the liver. These results suggest that the growth retardation caused by leucine imbalance was mainly because of the suppression of food intake, and demonstrated that there are no causal relationships between ASNS, PHGDH and SDS expression and amino acid imbalance caused by leucine.
[Mh] Termos MeSH primário: Aspartato-Amônia Ligase/metabolismo
Dieta
Ingestão de Alimentos/efeitos dos fármacos
L-Serina Desidratase/metabolismo
Leucina/efeitos adversos
Fígado/efeitos dos fármacos
Fosfoglicerato Desidrogenase/metabolismo
[Mh] Termos MeSH secundário: Aminoácidos/administração & dosagem
Aminoácidos/metabolismo
Animais
Peso Corporal
Caseínas/administração & dosagem
Regulação para Baixo
Ingestão de Energia/efeitos dos fármacos
Crescimento/efeitos dos fármacos
Homeostase/efeitos dos fármacos
Isoleucina/farmacologia
Leucina/administração & dosagem
Fígado/metabolismo
Masculino
Ratos Sprague-Dawley
Ativação Transcricional
Regulação para Cima
Valina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amino Acids); 0 (Caseins); 04Y7590D77 (Isoleucine); EC 1.1.1.95 (Phosphoglycerate Dehydrogenase); EC 4.3.1.17 (L-Serine Dehydratase); EC 6.3.1.1 (Aspartate-Ammonia Ligase); GMW67QNF9C (Leucine); HG18B9YRS7 (Valine)
[Em] Mês de entrada:1611
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160216
[St] Status:MEDLINE
[do] DOI:10.3177/jnsv.61.441


  7 / 588 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26367174
[Au] Autor:Qin Z; Yan Q; Ma Q; Jiang Z
[Ad] Endereço:College of Food Science and Nutritional Engineering, Beijing Advanced Innovation Center of Food Nutrition and Human Health, China Agricultural University, Beijing 100083, China.
[Ti] Título:Crystal structure and characterization of a novel L-serine ammonia-lyase from Rhizomucor miehei.
[So] Source:Biochem Biophys Res Commun;466(3):431-7, 2015 Oct 23.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:L-serine ammonia-lyase, as a member of the ß-family of pyridoxal-5'-phosphate (PLP) dependent enzymes, catalyzes the conversion of L-serine (L-threonine) to pyruvate (α-ketobutyrate) and ammonia. The crystal structure of L-serine ammonia-lyase from Rhizomucor miehei (RmSDH) was solved at 1.76 Å resolution by X-ray diffraction method. The overall structure of RmSDH had the characteristic ß-family PLP dependent enzyme fold. It consisted of two distinct domains, both of which show the typical open twisted α/ß structure. A PLP cofactor was located in the crevice between the two domains, which was attached to Lys52 by a Schiff-base linkage. Unique residue substitutions (Gly78, Pro79, Ser146, Ser147 and Thr312) were discovered at the catalytic site of RmSDH by comparison of structures of RmSDH and other reported eukaryotic L-serine ammonia-lyases. Optimal pH and temperature of the purified RmSDH were 7.5 and 40 °C, respectively. It was stable in the pH range of 7.0-9.0 and at temperatures below 40 °C. This is the first crystal structure of a fungal L-serine ammonia-lyase. It will be useful to study the catalytic mechanism of ß-elimination enzymes and will provide a basis for further enzyme engineering.
[Mh] Termos MeSH primário: Proteínas Fúngicas/química
L-Serina Desidratase/química
Rhizomucor/enzimologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Substituição de Aminoácidos
Domínio Catalítico
Cristalografia por Raios X
Proteínas Fúngicas/genética
Proteínas Fúngicas/metabolismo
L-Serina Desidratase/genética
L-Serina Desidratase/metabolismo
Modelos Moleculares
Dados de Sequência Molecular
Estrutura Terciária de Proteína
Fosfato de Piridoxal/metabolismo
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Rhizomucor/genética
Homologia de Sequência de Aminoácidos
Homologia Estrutural de Proteína
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Fungal Proteins); 0 (Recombinant Proteins); 5V5IOJ8338 (Pyridoxal Phosphate); EC 4.3.1.17 (L-Serine Dehydratase)
[Em] Mês de entrada:1604
[Cu] Atualização por classe:151005
[Lr] Data última revisão:
151005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150915
[St] Status:MEDLINE


  8 / 588 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26266572
[Au] Autor:Yan Y; Grant GA; Gross ML
[Ad] Endereço:Department of Chemistry, Washington University , One Brookings Drive, Box 1134, St. Louis, Missouri 63130, United States.
[Ti] Título:Hydrogen-Deuterium Exchange Mass Spectrometry Reveals Unique Conformational and Chemical Transformations Occurring upon [4Fe-4S] Cluster Binding in the Type 2 L-Serine Dehydratase from Legionella pneumophila.
[So] Source:Biochemistry;54(34):5322-8, 2015 Sep 01.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The type 2 L-serine dehydratase from Legionella pneumophila (lpLSD) contains a [4Fe-4S](2+) cluster that acts as a Lewis acid to extract the hydroxyl group of L-serine during the dehydration reaction. Surprisingly, the crystal structure shows that all four of the iron atoms in the cluster are coordinated with protein cysteinyl residues and that the cluster is buried and not exposed to solvent. If the crystal structure of lpLSD accurately reflects the structure in solution, then substantial rearrangement at the active site is necessary for the substrate to enter. Furthermore, repair of the oxidized protein when the cluster has degraded would presumably entail exposure of the buried cysteine ligands. Thus, the conformation required for the substrate to enter may be similar to those required for a new cluster to enter the active site. To address this, hydrogen-deuterium exchange combined with mass spectrometry (HDX MS) was used to probe the conformational changes that occur upon oxidative degradation of the Fe-S cluster. The regions that show the most significant differential HDX are adjacent to the cluster location in the holoenzyme or connect regions that are adjacent to the cluster. The observed decrease in flexibility upon cluster binding provides direct evidence that the "tail-in-mouth" conformation observed in the crystal structure also occurs in solution and that the C-terminal peptide is coordinated to the [4Fe-4S] cluster in a precatalytic conformation. This observation is consistent with the requirement of an activation step prior to catalysis and the unusually high level of resistance to oxygen-induced cluster degradation. Furthermore, peptide mapping of the apo form under nonreducing conditions revealed the formation of disulfide bonds between C396 and C485 and possibly between C343 and C385. These observations provide a picture of how the cluster loci are stabilized and poised to receive the cluster in the apo form and the requirement for a reduction step during cluster formation.
[Mh] Termos MeSH primário: Proteínas de Bactérias/química
L-Serina Desidratase/química
Legionella pneumophila/enzimologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Domínio Catalítico
Medição da Troca de Deutério
Holoenzimas/química
Holoenzimas/genética
Holoenzimas/metabolismo
Proteínas com Ferro-Enxofre/química
L-Serina Desidratase/genética
L-Serina Desidratase/metabolismo
Legionella pneumophila/genética
Espectrometria de Massas
Modelos Moleculares
Dados de Sequência Molecular
Mapeamento de Peptídeos
Ligação Proteica
Conformação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Holoenzymes); 0 (Iron-Sulfur Proteins); EC 4.3.1.17 (L-Serine Dehydratase)
[Em] Mês de entrada:1511
[Cu] Atualização por classe:150901
[Lr] Data última revisão:
150901
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150813
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.5b00761


  9 / 588 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:25617179
[Au] Autor:Ito T; Takada H; Isobe K; Suzuki M; Kitaura Y; Hemmi H; Matsuda T; Sasabe J; Yoshimura T
[Ad] Endereço:Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Furou-chou, Chikusa, Nagoya, Aichi 464-8601, Japan.
[Ti] Título:PEGylated D-serine dehydratase as a D-serine reducing agent.
[So] Source:J Pharm Biomed Anal;116:34-9, 2015 Dec 10.
[Is] ISSN:1873-264X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:D-Serine is an endogenous coagonist for N-methyl-D-aspartate (NMDA) receptors and is involved in excitatory neurotransmission. Excessive receptor activation causes excitotoxicity, leading to various acute and chronic neurological disorders. Decrease in D-serine content may provide a therapeutic strategy for the treatment of the neurological disorders in which overstimulation of NMDA receptors plays a pathological role. Saccharomyces cerevisiaed-serine dehydratase (Dsd1p), which acts dominantly on D-serine, may be a useful D-serine reducing agent. We conjugated a linear 5-kDa polyethylene glycol (PEG) to Dsd1p (PEG-Dsd1p) and examined the effects of PEG-conjugation on its biochemical and pharmacokinetic properties. PEG-Dsd1p retained activity, specificity, and stability of the enzyme. The PEG modification extended the serum half-life of Dsd1p in mice 6-fold, from 3.8h to 22.4h. PEG-Dsd1p was much less immunogenic compared to the unmodified enzyme. Intraperitoneal administration of PEG-Dsd1p was effective in decreasing the D-serine content in the mouse hippocampus. These findings suggest that PEG-Dsd1p may be a novel tool for lowering D-serine levels in vivo.
[Mh] Termos MeSH primário: L-Serina Desidratase/metabolismo
Polietilenoglicóis/metabolismo
Substâncias Redutoras/metabolismo
Serina/metabolismo
[Mh] Termos MeSH secundário: Animais
Feminino
Hipocampo/efeitos dos fármacos
Hipocampo/metabolismo
L-Serina Desidratase/química
L-Serina Desidratase/farmacologia
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C57BL
Camundongos Endogâmicos ICR
Polietilenoglicóis/química
Polietilenoglicóis/farmacologia
Substâncias Redutoras/química
Serina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Reducing Agents); 30IQX730WE (Polyethylene Glycols); 452VLY9402 (Serine); EC 4.3.1.17 (L-Serine Dehydratase)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:151020
[Lr] Data última revisão:
151020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150125
[St] Status:MEDLINE


  10 / 588 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:25510247
[Au] Autor:Zhang Y; Lin Z; Liu Q; Li Y; Wang Z; Ma H; Chen T; Zhao X
[Ad] Endereço:Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, 300072, People's Republic of China. zhangyan12@tju.edu.cn.
[Ti] Título:Engineering of Serine-Deamination pathway, Entner-Doudoroff pathway and pyruvate dehydrogenase complex to improve poly(3-hydroxybutyrate) production in Escherichia coli.
[So] Source:Microb Cell Fact;13:172, 2014 Dec 16.
[Is] ISSN:1475-2859
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Poly(3-hydroxybutyrate) (PHB), a biodegradable bio-plastic, is one of the most common homopolymer of polyhydroxyalkanoates (PHAs). PHB is synthesized by a variety of microorganisms as intracellular carbon and energy storage compounds in response to environmental stresses. Bio-based production of PHB from renewable feedstock is a promising and sustainable alternative to the petroleum-based chemical synthesis of plastics. In this study, a novel strategy was applied to improve the PHB biosynthesis from different carbon sources. RESULTS: In this research, we have constructed E. coli strains to produce PHB by engineering the Serine-Deamination (SD) pathway, the Entner-Doudoroff (ED) pathway, and the pyruvate dehydrogenase (PDH) complex. Firstly, co-overexpression of sdaA (encodes L-serine deaminase), L-serine biosynthesis genes and pgk (encodes phosphoglycerate kinase) activated the SD Pathway, and the resulting strain SD02 (pBHR68), harboring the PHB biosynthesis genes from Ralstonia eutropha, produced 4.86 g/L PHB using glucose as the sole carbon source, representing a 2.34-fold increase compared to the reference strain. In addition, activating the ED pathway together with overexpressing the PDH complex further increased the PHB production to 5.54 g/L with content of 81.1% CDW. The intracellular acetyl-CoA concentration and the [NADPH]/[NADP(+)] ratio were enhanced after the modification of SD pathway, ED pathway and the PDH complex. Meanwhile, these engineering strains also had a significant increase in PHB concentration and content when xylose or glycerol was used as carbon source. CONCLUSIONS: Significant levels of PHB biosynthesis from different kinds of carbon sources can be achieved by engineering the Serine-Deamination pathway, Entner-Doudoroff pathway and pyruvate dehydrogenase complex in E. coli JM109 harboring the PHB biosynthesis genes from Ralstonia eutropha. This work demonstrates a novel strategy for improving PHB production in E. coli. The strategy reported here should be useful for the bio-based production of PHB from renewable resources.
[Mh] Termos MeSH primário: Proteínas de Bactérias
Cupriavidus necator
Escherichia coli
Hidroxibutiratos/metabolismo
Engenharia Metabólica
Poliésteres/metabolismo
[Mh] Termos MeSH secundário: Proteínas de Bactérias/biossíntese
Proteínas de Bactérias/genética
Cupriavidus necator/enzimologia
Cupriavidus necator/genética
Escherichia coli/enzimologia
Escherichia coli/genética
L-Serina Desidratase/biossíntese
L-Serina Desidratase/genética
Fosfoglicerato Quinase/biossíntese
Fosfoglicerato Quinase/genética
Complexo Piruvato Desidrogenase/genética
Complexo Piruvato Desidrogenase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Hydroxybutyrates); 0 (Polyesters); 0 (Pyruvate Dehydrogenase Complex); 26063-00-3 (poly-beta-hydroxybutyrate); EC 2.7.2.3 (Phosphoglycerate Kinase); EC 4.3.1.17 (L-Serine Dehydratase)
[Em] Mês de entrada:1510
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141217
[St] Status:MEDLINE
[do] DOI:10.1186/s12934-014-0172-6



página 1 de 59 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