Base de dados : MEDLINE
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  1 / 8994 MEDLINE  
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[PMID]:29338056
[Au] Autor:Tien C; Huang L; Watanabe SM; Speidel JT; Carter CA; Chen C
[Ad] Endereço:Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado, United States of America.
[Ti] Título:Context-dependent autoprocessing of human immunodeficiency virus type 1 protease precursors.
[So] Source:PLoS One;13(1):e0191372, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:HIV-1 protease autoprocessing is responsible for liberation of free mature protease (PR) from the Gag-Pol polyprotein precursor. A cell-based model system was previously developed to examine the autoprocessing mechanism of fusion precursors carrying the p6*-PR miniprecursor sandwiched between various proteins or epitopes. We here report that precursor autoprocessing is context-dependent as its activity and outcomes can be modulated by sequences upstream of p6*-PR. This was exemplified by the 26aa maltose binding protein (MBP) signal peptide (SigP) when placed at the N-terminus of a fusion precursor. The mature PRs released from SigP-carrying precursors are resistant to self-degradation whereas those released from SigP-lacking fusion precursors are prone to self-degradation. A H69D mutation in PR abolished autoprocessing of SigP-containing fusion precursors whereas it only partially suppressed autoprocessing of fusion precursors lacking SigP. An autoprocessing deficient GFP fusion precursor with SigP exhibited a subcellular distribution pattern distinct from the one without it in transfected HeLa cells. Furthermore, a SigP fusion precursor carrying a substitution at the P1 position released the mature PR and PR-containing fragments that were different from those released from the precursor carrying the same mutation but lacking SigP. We also examined autoprocessing outcomes in viral particles produced by a NL4-3 derived proviral construct and demonstrated the existence of several PR-containing fragments along with the mature PR. Some of these resembled the SigP precursor autoprocessing outcomes. This finding of context-dependent modulation reveals the complexity of precursor autoprocessing regulation that most likely accompanies sequence variation imposed by the evolution of the upstream Gag moiety.
[Mh] Termos MeSH primário: Precursores Enzimáticos/metabolismo
Protease de HIV/metabolismo
HIV-1/enzimologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Precursores Enzimáticos/química
Precursores Enzimáticos/genética
Células HEK293
Protease de HIV/química
Protease de HIV/genética
Seres Humanos
Mutação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Enzyme Precursors); EC 3.4.23.- (HIV Protease); EC 3.4.23.- (p16 protease, Human immunodeficiency virus 1)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191372


  2 / 8994 MEDLINE  
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[PMID]:29193264
[Au] Autor:Kausar S; Abbas MN; Qian C; Zhu B; Gao J; Sun Y; Wang L; Wei G; Liu C
[Ad] Endereço:College of Life Sciences, Anhui Agricultural University, Hefei, China.
[Ti] Título:Role of Antheraea pernyi serpin 12 in prophenoloxidase activation and immune responses.
[So] Source:Arch Insect Biochem Physiol;97(2), 2018 Feb.
[Is] ISSN:1520-6327
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Serine protease inhibitors play a key role in the immune system of invertebrates by controlling proteolytic cascades. Besides its importance, the knowledge on immune functions of serpins in most of insects is fragmentary. In the present study, we identified serpin-12 from Antheraea pernyi encoding a predicted 402 amino acid residue protein (Apserpin-12). We expressed the recombinant protein in Escherichia coli and the purified protein was used for the synthesis of rabbit anti-Apserpin-12 polyclonal antibodies and functional studies. Quantitative real-time ploymerase chain reaction (qRT-PCR) analysis revealed that the knock-down of Apserpin-12 enhanced the prophenoloxidase (PPO) cascade stimulated by Micrococcus luteus in hemolymph, whereas addition of recombinant Apserpin-12 protein along with same elicitor led to down-regulate PPO activation. Following different microbial challenge (E. coli, Beauveria bassiana, M. Luteus, and nuclear polyhedrosis virus), the expression of Apserpin-12 mRNA was induced significantly. Furthermore, the Apserpin-12 double-stranded RNA administration elicited the expression of antimicrobial peptides, while the treatment with recombinant protein suppressed their expression. Tissue profile of Apserpin-12 indicated that it is expressed in all examined tissues, that is, hemolymph, malpighian tubules, midgut, silk gland, integument, and fat body with variation in their transcript levels. We concluded that Apserpin-12 may regulate PPO activation and inhibit the production of antimicrobial peptides in A. pernyi, suggesting important role in its immune system.
[Mh] Termos MeSH primário: Catecol Oxidase/metabolismo
Precursores Enzimáticos/metabolismo
Mariposas/química
Serpinas/isolamento & purificação
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Peptídeos Catiônicos Antimicrobianos/metabolismo
Ativação Enzimática
Escherichia coli
Mariposas/fisiologia
Filogenia
Serpinas/química
Serpinas/genética
Serpinas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimicrobial Cationic Peptides); 0 (Enzyme Precursors); 0 (Serpins); EC 1.10.3.- (pro-phenoloxidase); EC 1.10.3.1 (Catechol Oxidase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171202
[St] Status:MEDLINE
[do] DOI:10.1002/arch.21435


  3 / 8994 MEDLINE  
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[PMID]:29329315
[Au] Autor:Kumar S; Cieplak P
[Ad] Endereço:SBP Medical Discovery Institute, La Jolla, California, United States of America.
[Ti] Título:Role of N-glycosylation in activation of proMMP-9. A molecular dynamics simulations study.
[So] Source:PLoS One;13(1):e0191157, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human matrix metalloproteinase proMMP-9 is secreted as latent zymogen, which requires two-steps proteolytic activation. The secreted proMMP-9 is glycosylated at two positions: Asn38 and Asn120 located in the prodomain and catalytic domain, respectively. It has been demonstrated that glycosylation at Asn120 is required for secretion of the enzyme, while the role of Asn38 glycosylation is not well understood, but is usually linked to the activation process. One hypothesis stated that the Asn38 glycosylation might protect against proteolytic activation. However, the activation process occurs with or without the presence of this glycosylation. We conducted molecular dynamics (MD) simulations on the glycosylated and non-glycosylated proMMP-9 to elucidate the effect of Asn38 glycosylation on this two-step activation process. The simulation results suggest that Asn38 glycosylation does not hinder the activation process directly, but induces conformational changes in the vicinity of the first proteolytic region in such a way that E59-M60 cleavage is processed before R106-F107. These results correlate with analysis provided by Boon et al. and experimental data from Ogata et al. who attempted to determine the order of events in activation of proMMP-9. Results from additional MD simulations for the model of glycosylated proMMP-9 bound to galectin-8 N-domain suggest that Gal-8 by interacting with Asn38 glycan might further facilitate processing of the first cleavage between E59-M60. Thus, our simulation results suggest that both Asn38 glycosylation and interaction with Gal-8N may be involved in facilitating and the temporal order of the activation process of pro-MMP9. The aim of this report is to provide an inspiration for future detailed experiments aimed at explaining the role of N-glycosylation in the activation process of prodomain of MMP-9.
[Mh] Termos MeSH primário: Precursores Enzimáticos/metabolismo
Metaloproteinase 9 da Matriz/metabolismo
Simulação de Dinâmica Molecular
[Mh] Termos MeSH secundário: Ativação Enzimática
Glicosilação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Enzyme Precursors); EC 3.4.24.35 (Matrix Metalloproteinase 9)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180113
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191157


  4 / 8994 MEDLINE  
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[PMID]:28452589
[Au] Autor:Griner JD; Rogers CJ; Zhu MJ; Du M
[Ad] Endereço:a Department of Animal Sciences , Washington State University , Pullman , WA , USA.
[Ti] Título:Lysyl oxidase propeptide promotes adipogenesis through inhibition of FGF-2 signaling.
[So] Source:Adipocyte;6(1):12-19, 2017 01 02.
[Is] ISSN:2162-397X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Lysyl oxidase (LOX) catalyzes the oxidative deamination of lysine residues in collagen and elastin, key components of connective tissue. LOX is synthesized as an inactive 50 kD pre-proenzyme, and secreted to the extracellular matrix where it is cleaved into an active 32 kD LOX, and an 18kD free propeptide (LOX-PP), purportedly an inhibitor of fibroblast growth factor-2 (FGF-2) signaling. Given that adipocytes are distributed inside the connective tissue, it is likely that LOX-PP has an important regulatory role in adipogenesis, which has not been studied. Using NIH 3T3-L1 cells, we observed that FGF-2 inhibited adipogenesis, and LOX-PP promoted adipogenesis of 3T3-L1 cells in the presence of FGF-2; the expression of peroxisome proliferator-activated receptor (PPAR) γ and CCAAT-enhancer binding protein (C/EBP) α, two markers of adipogenesis, were enhanced in the presence of LOX-PP. We further observed that LOX-PP down-regulated AKT and ERK1/2, two proliferative signaling proteins down-stream of FGF-2 signaling. Similarly, inhibition of FGF-2 receptor signaling by canofin, a competitive inhibitor of FGF-2 receptor, promoted adipogenesis albeit less effective compared to LOX-PP. To further explore whether LOX-PP promoted adipogenesis through inhibition of FGF-2 signaling, site directed mutagenesis of LOX-PP, resulting in an Arg158 to Gln158 mutation which abolishes the inhibitory activity of LOX-PP to FGF-2 receptor, attenuated the adipogenic promoting properties of LOX-PP. In summary, for the first time, our data show that LOX-PP enhances adipogenesis at least partially through inhibition of FGF-2 receptor signaling. Our data suggest that LOX-PP may serve as a bona fide therapeutic target for regulating adipogenesis and adipose tissue development.
[Mh] Termos MeSH primário: Adipogenia/fisiologia
Proteína-Lisina 6-Oxidase/biossíntese
Proteína-Lisina 6-Oxidase/metabolismo
[Mh] Termos MeSH secundário: Células 3T3-L1
Adipócitos/metabolismo
Animais
Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo
Proliferação Celular/fisiologia
Colágeno/metabolismo
Elastina/metabolismo
Precursores Enzimáticos/metabolismo
Fator 2 de Crescimento de Fibroblastos/antagonistas & inibidores
Fator 2 de Crescimento de Fibroblastos/metabolismo
Fator 2 de Crescimento de Fibroblastos/fisiologia
Lisina/metabolismo
Camundongos
PPAR gama/metabolismo
Proteína-Lisina 6-Oxidase/química
Transdução de Sinais/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CCAAT-Enhancer-Binding Protein-alpha); 0 (Enzyme Precursors); 0 (PPAR gamma); 103107-01-3 (Fibroblast Growth Factor 2); 9007-34-5 (Collagen); 9007-58-3 (Elastin); EC 1.4.3.13 (Protein-Lysine 6-Oxidase); K3Z4F929H6 (Lysine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1080/21623945.2016.1271511


  5 / 8994 MEDLINE  
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[PMID]:28867563
[Au] Autor:Tong Q; Zhang M; Cao X; Xu S; Wang D; Zhao Y
[Ad] Endereço:School of Marine Sciences, Ningbo University, Ningbo 315211, China.
[Ti] Título:Expression and activation of Daphnia pulex Caspase-3 are involved in regulation of aging.
[So] Source:Gene;634:37-46, 2017 Nov 15.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Death-mediating proteases such as Caspases have been implicated in aging. Remarkably, active Caspase-3 can trigger widespread damage and degeneration, playing a key role in causing cell death. In order to explore the relationship between Caspase-3 and aging in Daphnia pulex, we cloned and analyzed the full-length cDNA sequence of its Caspase-3 gene. Both mRNA expression and activity of D. pulex Caspase-3 increased with age. Moreover, different forms of Caspase-3 appeared with aging. The expression of casp3-L was higher and decreased with age, while that of casp3-S was weak and increased with age, consistent with the trend in Caspase-3 activity. Mhc mRNA expression declined over time and was negatively correlated with age and Caspase-3. In situ hybridization results showed that Caspase-3 mRNA was expressed in different growth and reproduction stages, and its expression levels in embryos and larva were lower than that in adult D. pulex. Western blot analysis revealed the presence of Caspase-3 in the form of zymogens with a molecular weight of ~36kDa. Overall, this study explored age-associated gene regulation to provide a basis for the molecular mechanism of D. pulex reproductive conversion.
[Mh] Termos MeSH primário: Envelhecimento/genética
Caspase 3/genética
Caspase 3/metabolismo
Daphnia/fisiologia
[Mh] Termos MeSH secundário: Envelhecimento/metabolismo
Animais
Proteínas de Artrópodes/química
Proteínas de Artrópodes/genética
Proteínas de Artrópodes/metabolismo
Caspase 3/química
Clonagem Molecular
Daphnia/genética
Precursores Enzimáticos/metabolismo
Regulação da Expressão Gênica no Desenvolvimento
Modelos Moleculares
Peso Molecular
Filogenia
Análise de Sequência de DNA
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Arthropod Proteins); 0 (Enzyme Precursors); EC 3.4.22.- (Caspase 3)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170905
[St] Status:MEDLINE


  6 / 8994 MEDLINE  
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[PMID]:28860188
[Au] Autor:Scannevin RH; Alexander R; Haarlander TM; Burke SL; Singer M; Huo C; Zhang YM; Maguire D; Spurlino J; Deckman I; Carroll KI; Lewandowski F; Devine E; Dzordzorme K; Tounge B; Milligan C; Bayoumy S; Williams R; Schalk-Hihi C; Leonard K; Jackson P; Todd M; Kuo LC; Rhodes KJ
[Ad] Endereço:From Janssen Research and Development, LLC, Spring House, Pennsylvania 19477 rscannevin@yumanity.com.
[Ti] Título:Discovery of a highly selective chemical inhibitor of matrix metalloproteinase-9 (MMP-9) that allosterically inhibits zymogen activation.
[So] Source:J Biol Chem;292(43):17963-17974, 2017 Oct 27.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Aberrant activation of matrix metalloproteinases (MMPs) is a common feature of pathological cascades observed in diverse disorders, such as cancer, fibrosis, immune dysregulation, and neurodegenerative diseases. MMP-9, in particular, is highly dynamically regulated in several pathological processes. Development of MMP inhibitors has therefore been an attractive strategy for therapeutic intervention. However, a long history of failed clinical trials has demonstrated that broad-spectrum MMP inhibitors have limited clinical utility, which has spurred the development of inhibitors selective for individual MMPs. Attaining selectivity has been technically challenging because of sequence and structural conservation across the various MMPs. Here, through a biochemical and structural screening paradigm, we have identified JNJ0966, a highly selective compound that inhibited activation of MMP-9 zymogen and subsequent generation of catalytically active enzyme. JNJ0966 had no effect on MMP-1, MMP-2, MMP-3, MMP-9, or MMP-14 catalytic activity and did not inhibit activation of the highly related MMP-2 zymogen. The molecular basis for this activity was characterized as an interaction of JNJ0966 with a structural pocket in proximity to the MMP-9 zymogen cleavage site near Arg-106, which is distinct from the catalytic domain. JNJ0966 was efficacious in reducing disease severity in a mouse experimental autoimmune encephalomyelitis model, demonstrating the viability of this therapeutic approach. This discovery reveals an unprecedented pharmacological approach to MMP inhibition, providing an opportunity to improve selectivity of future clinical drug candidates. Targeting zymogen activation in this manner may also allow for pharmaceutical exploration of other enzymes previously viewed as intractable drug targets.
[Mh] Termos MeSH primário: Precursores Enzimáticos/antagonistas & inibidores
Precursores Enzimáticos/química
Metaloproteinase 9 da Matriz/química
Inibidores de Metaloproteinases de Matriz/química
[Mh] Termos MeSH secundário: Regulação Alostérica
Animais
Células COS
Domínio Catalítico
Cercopithecus aethiops
Precursores Enzimáticos/genética
Precursores Enzimáticos/metabolismo
Seres Humanos
Metaloproteinase 9 da Matriz/genética
Metaloproteinase 9 da Matriz/metabolismo
Domínios Proteicos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Precursors); 0 (Matrix Metalloproteinase Inhibitors); EC 3.4.24.- (pro-matrix metalloproteinase 9); EC 3.4.24.35 (MMP9 protein, human); EC 3.4.24.35 (Matrix Metalloproteinase 9)
[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:170902
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.806075


  7 / 8994 MEDLINE  
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[PMID]:28844653
[Au] Autor:Vogelweith F; Moret Y; Thiéry D; Delbac L; Moreau J
[Ad] Endereço:Johannes-Gutenberg University of Mainz, Institute of Organismic and Molecular Evolution, Behavioral Ecology and Social Evolution Group, Johannes-von-Müller-Weg 6, 55128 Mainz, Germany. Electronic address: fanny.vogelweith@gmail.com.
[Ti] Título:No evidence of an immune adjustment in response to a parasitoid threat in Lobesia botrana larvae.
[So] Source:J Insect Physiol;102:7-11, 2017 Oct.
[Is] ISSN:1879-1611
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Immune function is a key determinant of an organism's fitness, and natural insect populations are highly variable for this trait, mainly due to environmental heterogeneity and pathogen diversity. We previously reported a positive correlation between infection prevalence by parasitoids and host immunity in natural populations of the vineyard pest Lobesia botrana. Here, we tested whether this correlation reflects a plastic adjustment of host immunity in response to the local presence of parasites. To this end, we measured immunity of non-parasitized L. botrana larvae exposed, respectively, to one of the two most common species of parasitoids in vineyards, over 6days. Larvae were able to sense the parasitoid through visual, chemical, or mechanical cues, but contact larvae-parasitoid were excluded. Contrary to our hypothesis, we found that L. botrana larvae did not increase their immune defenses in the presence of parasitoids, despite their ability to sense a potential threat. Our results therefore suggest that the positive correlation between infection prevalence by parasitoids and L. botrana immunity among natural populations may result from micro-evolutionary changes resulting from long-term local selection pressures imposed by parasitoids in wild populations rather than plastic adjustments of immunity.
[Mh] Termos MeSH primário: Mariposas/imunologia
Mariposas/parasitologia
Vespas/fisiologia
[Mh] Termos MeSH secundário: Animais
Catecol Oxidase/metabolismo
Precursores Enzimáticos/metabolismo
Hemócitos/metabolismo
Proteínas de Insetos/metabolismo
Larva/crescimento & desenvolvimento
Larva/imunologia
Larva/parasitologia
Larva/fisiologia
Mariposas/crescimento & desenvolvimento
Vespas/crescimento & desenvolvimento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Precursors); 0 (Insect Proteins); EC 1.10.3.- (pro-phenoloxidase); EC 1.10.3.1 (Catechol Oxidase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170829
[St] Status:MEDLINE


  8 / 8994 MEDLINE  
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[PMID]:28829816
[Au] Autor:Tseng CC; Jia B; Barndt R; Gu Y; Chen CY; Tseng IC; Su SF; Wang JK; Johnson MD; Lin CY
[Ad] Endereço:Lombardi Comprehensive Cancer Center, Department of Oncology Georgetown University, Washington DC, United States of America.
[Ti] Título:Matriptase shedding is closely coupled with matriptase zymogen activation and requires de novo proteolytic cleavage likely involving its own activity.
[So] Source:PLoS One;12(8):e0183507, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The type 2 transmembrane serine protease matriptase is involved in many pathophysiological processes probably via its enzymatic activity, which depends on the dynamic relationship between zymogen activation and protease inhibition. Matriptase shedding can prolong the life of enzymatically active matriptase and increase accessibility to substrates. We show here that matriptase shedding occurs via a de novo proteolytic cleavage at sites located between the SEA domain and the CUB domain. Point or combined mutations at the four positively charged amino acid residues in the region following the SEA domain allowed Arg-186 to be identified as the primary cleavage site responsible for matriptase shedding. Kinetic studies further demonstrate that matriptase shedding is temporally coupled with matriptase zymogen activation. The onset of matriptase shedding lags one minute behind matriptase zymogen activation. Studies with active site triad Ser-805 point mutated matriptase, which no longer undergoes zymogen activation or shedding, further suggests that matriptase shedding depends on matriptase zymogen activation, and that matriptase proteolytic activity may be involved in its own shedding. Our studies uncover an autonomous mechanism coupling matriptase zymogen activation, proteolytic activity, and shedding such that a proportion of newly generated active matriptase escapes HAI-1-mediated rapid inhibition by shedding into the extracellular milieu.
[Mh] Termos MeSH primário: Precursores Enzimáticos/metabolismo
Serina Endopeptidases/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Anticorpos Monoclonais/imunologia
Linhagem Celular Tumoral
Ativação Enzimática
Seres Humanos
Mutação Puntual
Proteólise
Homologia de Sequência de Aminoácidos
Serina Endopeptidases/química
Serina Endopeptidases/genética
Serina Endopeptidases/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Enzyme Precursors); EC 3.4.21.- (Serine Endopeptidases); EC 3.4.21.- (matriptase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170823
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183507


  9 / 8994 MEDLINE  
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[PMID]:28765284
[Au] Autor:Oda T; Hirabayashi H; Shikauchi G; Takamura R; Hiraga K; Minami H; Hashimoto H; Yamamoto M; Wakabayashi K; Shimizu T; Sato M
[Ad] Endereço:From the Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
[Ti] Título:Structural basis of autoinhibition and activation of the DNA-targeting ADP-ribosyltransferase pierisin-1.
[So] Source:J Biol Chem;292(37):15445-15455, 2017 Sep 15.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:ADP-ribosyltransferases transfer the ADP-ribose moiety of ßNAD to an acceptor molecule, usually a protein that modulates the function of the acceptor. Pierisin-1 is an ADP-ribosyltransferase from the cabbage butterfly and is composed of N-terminal catalytic and C-terminal ricin B-like domains. Curiously, it ADP-ribosylates the DNA duplex, resulting in apoptosis of various cancer cells, which has raised interest in pierisin-1 as an anti-cancer agent. However, both the structure and the mechanism of DNA ADP-ribosylation are unclear. Here, we report the crystal structures of the N-terminal catalytic domain of pierisin-1, its complex with ßNAD , and the catalytic domain with the linker connecting it to the ricin B-like domains. We found that the catalytic domain possesses a defined, positively charged region on the molecular surface but that its overall structure is otherwise similar to those of protein-targeting ADP-ribosyltransferases. Electrophoretic mobility shift assays and site-directed mutagenesis indicated that pierisin-1 binds double-stranded but not single-stranded DNA and that Lys , Lys , and Lys , which are found in a loop, and Arg and Arg , located in a basic cleft near the loop, are required for DNA binding. Furthermore, the structure of the catalytic domain with the linker revealed an autoinhibitory mechanism in which the linker occupies and blocks both the ßNAD - and DNA-binding sites, suggesting that proteolytic cleavage to remove the linker is necessary for enzyme catalysis. Our study provides a structural basis for the DNA-acceptor specificity of pierisin-1 and reveals that a self-regulatory mechanism is required for its activity.
[Mh] Termos MeSH primário: ADP Ribose Transferases/metabolismo
Borboletas/enzimologia
DNA/metabolismo
Precursores Enzimáticos/metabolismo
Proteínas de Insetos/metabolismo
Modelos Moleculares
NAD/metabolismo
Processamento de Proteína Pós-Traducional
[Mh] Termos MeSH secundário: ADP Ribose Transferases/química
ADP Ribose Transferases/genética
Substituição de Aminoácidos
Animais
Sítios de Ligação
Biocatálise
Domínio Catalítico
Cristalografia por Raios X
DNA/química
Ensaio de Desvio de Mobilidade Eletroforética
Ativação Enzimática
Precursores Enzimáticos/química
Precursores Enzimáticos/genética
Proteínas de Insetos/química
Proteínas de Insetos/genética
Mutagênese Sítio-Dirigida
Mutação
NAD/química
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Conformação Proteica
Domínios e Motivos de Interação entre Proteínas
Proteólise
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/metabolismo
Homologia Estrutural de Proteína
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Precursors); 0 (Insect Proteins); 0 (Peptide Fragments); 0 (Recombinant Fusion Proteins); 0 (pierisin protein, insect); 0U46U6E8UK (NAD); 9007-49-2 (DNA); EC 2.4.2.- (ADP Ribose Transferases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170927
[Lr] Data última revisão:
170927
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170803
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.776641


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[PMID]:28760669
[Au] Autor:Rouzet A; Reboux G; Dalphin JC; Gondouin A; De Vuyst P; Balliau T; Millon L; Valot B; Roussel S
[Ad] Endereço:UMR/CNRS 6249 Chrono-Environnement, University of Bourgogne Franche-Comté, UFR Sciences médicales et pharmaceutiques, 19 rue Ambroise Paré, 25030 Besançon, France. Electronic address: adeline.rouzet@univ-fcomte.fr.
[Ti] Título:An immunoproteomic approach revealed antigenic proteins enhancing serodiagnosis performance of bird fancier's lung.
[So] Source:J Immunol Methods;450:58-65, 2017 Nov.
[Is] ISSN:1872-7905
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Bird fancier's lung (BFL) caused by repeated inhalation of avian proteins is the most common form of hypersensitivity pneumonitis. However, the exact identification of proteins involved is unknown, and serological test use for diagnosis need to be standardized. The objectives of this study were (i) to identify antigenic proteins from pigeon droppings (ii) to provide information about their location in avian matrices and (iii) to produce them in recombinant proteins to evaluate their diagnostic performances. METHOD: Antigenic proteins of pigeon dropping extracts were investigated using 2-dimensional immunoblotting with sera from patients with BFL, asymptomatic exposed controls and healthy volunteers. We investigated the origin of these antigenic proteins by analyzing droppings, blooms and sera using a shotgun proteomic analysis. BFL-associated proteins were produced as recombinant antigens in E. coli and were assessed in ELISA with sera from patients (n=25) and subject exposed controls (n=30). These diagnostic performances were compared with those obtained by precipitin techniques (agar gel double diffusion, immunoelectrophoresis). RESULTS: We identified 14 antigenic proteins mainly located in droppings and blooms. These proteins were involved in either the digestive or immune systems of pigeons. Using the recombinant BFL-associated proteins: Immunoglobulin lambda-like polypeptide-1 (IGLL1: sensitivity: 76%; specificity: 100%; AUC: 0.93) and Proproteinase E (ProE: sensitivity: 84%; specificity: 80%; AUC: 0.85), the ELISA test showed better performance than precipitin assays with pigeon dropping extracts (sensitivity: 60%; specificity: 93.3%; AUC: 0.76). CONCLUSION: IGLL1 and ProE were identified as the biomarkers of the disease. The use of these highly standardized antigens discriminates BFL cases from exposed subjects in serological assays. The results of this study offer new possibilities for the serological diagnosis of the disease. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: Identifier NCT03056404.
[Mh] Termos MeSH primário: Alérgenos/imunologia
Proteínas Aviárias/imunologia
Pulmão dos Criadores de Aves/diagnóstico
Aves/imunologia
Ensaio de Imunoadsorção Enzimática
Fezes
Proteômica/métodos
Testes Sorológicos
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Animais
Área Sob a Curva
Pulmão dos Criadores de Aves/sangue
Pulmão dos Criadores de Aves/imunologia
Estudos de Casos e Controles
Cromatografia Líquida
Eletroforese em Gel de Ágar
Eletroforese em Gel Bidimensional
Endopeptidases/imunologia
Precursores Enzimáticos/imunologia
Feminino
Seres Humanos
Imunoeletroforese
Cadeias Leves Substitutas da Imunoglobulina/imunologia
Exposição por Inalação
Masculino
Meia-Idade
Valor Preditivo dos Testes
Curva ROC
Reprodutibilidade dos Testes
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Allergens); 0 (Avian Proteins); 0 (Enzyme Precursors); 0 (Immunoglobulin Light Chains, Surrogate); 0 (immunoglobulin lambda-like polypeptide 1, human); EC 3.4.- (Endopeptidases); EC 3.4.- (pro-proteinase E)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170802
[St] Status:MEDLINE



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