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Pesquisa : D08.811.913.696.900 [Categoria DeCS]
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[PMID]:29289611
[Au] Autor:Kazemi N; Estiar MA; Fazilaty H; Sakhinia E
[Ad] Endereço:Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Division of Medical Genetics, Department of Clinical Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
[Ti] Título:Variants in GNPTAB, GNPTG and NAGPA genes are associated with stutterers.
[So] Source:Gene;647:93-100, 2018 Mar 20.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Non-syndromic stuttering is a neurodevelopmental disorder characterized by disruptions in normal flow of speech in the form of repetition, prolongation and involuntary halts. Previously, mutations with more severe effects on GNPTAB and GNPTG have been reported to cause Mucolipidosisll (ML-ll) and Mucolipidosislll (ML-lll), two lysosomal storage disorders with multiple pathologies. We used homozygosity mapping and Sanger sequencing to investigate variants of the three genes in 25 Iranian families with at least two first degree related non-syndromic stutterers. Bioinformatic evaluation and Segregation analysis of the found variants helped us define probable consequences. We also compared our findings with those related to Mucolipidosis. 14 variations were found in the three genes 3 of which, including a novel variant within intronic region of GNPTG and a heterozygous 2-bp deletion in coding region of GNPTAB, co-segregated with stuttering in the families they were found. Bioinformatics analysis predicted all three variants causing deleterious effects on gene functioning. Our findings support the role of these three variants in non-syndromic stuttering. This finding may challenge the current belief that variations causing stuttering are at different sites and have less severe consequences than genetic changes that cause ML-ll and ML-lll.
[Mh] Termos MeSH primário: Predisposição Genética para Doença/genética
Mutação/genética
Diester Fosfórico Hidrolases/genética
Gagueira/genética
Transferases (Outros Grupos de Fosfato Substituídos)/genética
[Mh] Termos MeSH secundário: Criança
Pré-Escolar
Feminino
Heterozigoto
Homozigoto
Seres Humanos
Íntrons/genética
Masculino
Mucolipidoses/genética
Fenótipo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.7.8.- (Transferases (Other Substituted Phosphate Groups)); EC 2.7.8.15 (GNPTAB protein, human); EC 2.7.8.17 (GNPTG protein, human); EC 3.1.4.- (Phosphoric Diester Hydrolases); EC 3.1.4.45 (N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180209
[Lr] Data última revisão:
180209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180101
[St] Status:MEDLINE


  2 / 1252 MEDLINE  
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[PMID]:28742512
[Au] Autor:Chen Y; Cao Y
[Ad] Endereço:.
[Ti] Título:The sphingomyelin synthase family: proteins, diseases, and inhibitors.
[So] Source:Biol Chem;398(12):1319-1325, 2017 11 27.
[Is] ISSN:1437-4315
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Sphingomyelin (SM) is among the most important biomolecules in eukaryotes and acts as both constructive components and signal carrier in physiological processes. SM is catalyzed by a membrane protein family, sphingomyelin synthases (SMSs), consisting of three members, SMS1, SMS2 and SMSr. SMSs modulate sphingomyelin and other sphingolipids levels, thereby regulating membrane mobility, ceramide-dependent apoptosis and DAG-dependent signaling pathways. SMSs was found associated with various diseases. Downregulation of SMS2 activity results in protective effects against obesity, atherosclerosis and diabetes and makes SMS2 inhibitors potential medicines. Structural guided specific drug design could be the next breakthrough, discriminating SMS2 from other homologs.
[Mh] Termos MeSH primário: Aterosclerose/tratamento farmacológico
Diabetes Mellitus/tratamento farmacológico
Inibidores Enzimáticos/farmacologia
Obesidade/tratamento farmacológico
Transferases (Outros Grupos de Fosfato Substituídos)/antagonistas & inibidores
Transferases (Outros Grupos de Fosfato Substituídos)/metabolismo
[Mh] Termos MeSH secundário: Animais
Aterosclerose/metabolismo
Diabetes Mellitus/metabolismo
Inibidores Enzimáticos/química
Seres Humanos
Obesidade/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Enzyme Inhibitors); EC 2.7.8.- (Transferases (Other Substituted Phosphate Groups)); EC 2.7.8.- (phosphatidylcholine-ceramide phosphocholine transferase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE


  3 / 1252 MEDLINE  
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[PMID]:28724630
[Au] Autor:Aarnio-Peterson M; Zhao P; Yu SH; Christian C; Flanagan-Steet H; Wells L; Steet R
[Ad] Endereço:From the Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602.
[Ti] Título:Altered Met receptor phosphorylation and LRP1-mediated uptake in cells lacking carbohydrate-dependent lysosomal targeting.
[So] Source:J Biol Chem;292(36):15094-15104, 2017 Sep 08.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Acid hydrolases utilize a carbohydrate-dependent mechanism for lysosomal targeting. These hydrolases acquire a mannose 6-phosphate tag by the action of the GlcNAc-1-phosphotransferase enzyme, allowing them to bind receptors and traffic to endosomes. Loss of GlcNAc-1-phosphotransferase results in hydrolase hypersecretion and profound lysosomal storage. Little, however, is known about how these cellular phenotypes affect the trafficking, activity, and localization of surface glycoproteins. To address this question, we profiled the abundance of surface glycoproteins in WT and CRISPR-mediated HeLa cells and identified changes in numerous glycoproteins, including the uptake receptor LRP1 and multiple receptor tyrosine kinases. Decreased cell surface LRP1 in cells corresponded with a reduction in its steady-state level and less amyloid-ß-40 (Aß40) peptide uptake. cells displayed elevated activation of several kinases including Met receptor. We found increased Met phosphorylation within both the kinase and the docking domains and observed that lower concentrations of pervanadate were needed to cause an increase in phospho-Met in cells. Together, these data suggested a decrease in the activity of the receptor and non-receptor protein-tyrosine phosphatases that down-regulate Met phosphorylation. cells exhibited elevated levels of reactive oxygen species, known to inactivate cell surface and cytosolic phosphatases by oxidation of active site cysteine residues. Consistent with this mode of action, peroxide treatment of parental HeLa cells elevated phospho-Met levels whereas antioxidant treatment of cells reduced phospho-Met levels. Collectively, these findings identify new mechanisms whereby impaired lysosomal targeting can impact the activity and recycling of receptors.
[Mh] Termos MeSH primário: Carboidratos
Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo
Lisossomos/metabolismo
Proteínas Proto-Oncogênicas c-met/metabolismo
Transferases (Outros Grupos de Fosfato Substituídos)/metabolismo
[Mh] Termos MeSH secundário: Células HeLa
Seres Humanos
Fosforilação
Proteínas Proto-Oncogênicas c-met/química
Transferases (Outros Grupos de Fosfato Substituídos)/deficiência
Transferases (Outros Grupos de Fosfato Substituídos)/genética
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carbohydrates); 0 (LRP1 protein, human); 0 (Low Density Lipoprotein Receptor-Related Protein-1); EC 2.7.10.1 (Proto-Oncogene Proteins c-met); EC 2.7.8.- (Transferases (Other Substituted Phosphate Groups)); EC 2.7.8.15 (GNPTAB protein, human)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170721
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.790139


  4 / 1252 MEDLINE  
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[PMID]:28722191
[Au] Autor:Konno S; Ishikawa F; Suzuki T; Dohmae N; Kakeya H; Tanabe G
[Ad] Endereço:Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo, Kyoto, 606-8501, Japan.
[Ti] Título:A Chemoproteomics Approach to Investigate Phosphopantetheine Transferase Activity at the Cellular Level.
[So] Source:Chembiochem;18(18):1855-1862, 2017 Sep 19.
[Is] ISSN:1439-7633
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Phosphopantetheinylation is an essential post-translational protein modification to primary and secondary metabolic pathways that ensures bacterial cell viability and virulence, and it is used in the production of many pharmaceuticals. Traditional methods have not provided a comprehensive understanding of these modifications. By using chemical proteomic probes for adenylation and thiolation domains in nonribosomal peptide synthetases (NRPSs), chemoproteomics has been applied to survey and validate the cellular activity of 4-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-N-(4-methoxypyridin-2-yl)piperazine-1-carbothioamide (ML267), which is a potent and selective small-molecule 4'-phosphopantetheinyl transferase (PPTase) inhibitor that attenuates secondary metabolism and viability of bacterial cells. ML267 inhibited Sfp-type PPTase and antagonized phosphopantetheinylation in cells, which resulted in a decrease in phosphopantetheinylated NRPSs and the attenuation of Sfp-PPTase-dependent metabolite production. These results indicate that this chemoproteomics platform should enable a precise interpretation of the cellular activities of Sfp-type PPTase inhibitors.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Proteômica
Transferases (Outros Grupos de Fosfato Substituídos)/metabolismo
[Mh] Termos MeSH secundário: Antibacterianos/química
Antibacterianos/metabolismo
Antibacterianos/farmacologia
Bacillus subtilis/efeitos dos fármacos
Bacillus subtilis/enzimologia
Proteínas de Bactérias/antagonistas & inibidores
Lipopeptídeos/metabolismo
Peptídeo Sintases/análise
Peptídeo Sintases/metabolismo
Peptídeos Cíclicos/metabolismo
Ligação Proteica
Processamento de Proteína Pós-Traducional
Piridinas/química
Piridinas/metabolismo
Piridinas/farmacologia
Tioureia/análogos & derivados
Tioureia/química
Tioureia/metabolismo
Tioureia/farmacologia
Transferases (Outros Grupos de Fosfato Substituídos)/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (4-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-N-(4-methoxypyridin-2-yl)piperazine-1-carbothioamide); 0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (Lipopeptides); 0 (Peptides, Cyclic); 0 (Pyridines); 0 (phosphopantetheinyl transferase); 24730-31-2 (surfactin peptide); EC 2.7.8.- (Transferases (Other Substituted Phosphate Groups)); EC 6.3.2.- (Peptide Synthases); EC 6.3.2.- (non-ribosomal peptide synthase); GYV9AM2QAG (Thiourea)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170720
[St] Status:MEDLINE
[do] DOI:10.1002/cbic.201700301


  5 / 1252 MEDLINE  
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[PMID]:28619536
[Au] Autor:Qi XY; Cao Y; Li YL; Mo MG; Zhou L; Ye DY
[Ad] Endereço:Department of Medicinal Chemistry, School of Pharmacy, Fudan University, No. 826, Zhangheng Rd., Shanghai 201203, China.
[Ti] Título:Discovery of the selective sphingomyelin synthase 2 inhibitors with the novel structure of oxazolopyridine.
[So] Source:Bioorg Med Chem Lett;27(15):3511-3515, 2017 08 01.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Sphingomyelin synthase (SMS) is a key enzyme in sphingomyelin biosynthetic pathway, whose activity is highly related to the atherosclerosis progression. SMS2 could serve as a promising therapeutic target for atherosclerosis. Based on the structure of lead compound D2, a series of oxazolopyridine derivatives were designed, synthesized, and their inhibitory activities against purified SMS1 and SMS2 enzymes were evaluated respectively. The representative molecules QY4 and QY16 possess micromolar inhibitory activities against SMS2 and excellent isoform preferences over SMS1, qualified to be selected as potential molecules in further discovery of specific SMS2 inhibitors.
[Mh] Termos MeSH primário: Inibidores Enzimáticos/química
Inibidores Enzimáticos/farmacologia
Proteínas de Membrana/antagonistas & inibidores
Proteínas do Tecido Nervoso/antagonistas & inibidores
Piridinas/química
Piridinas/farmacologia
Transferases (Outros Grupos de Fosfato Substituídos)/antagonistas & inibidores
[Mh] Termos MeSH secundário: Descoberta de Drogas
Seres Humanos
Proteínas de Membrana/química
Proteínas de Membrana/metabolismo
Simulação de Acoplamento Molecular
Proteínas do Tecido Nervoso/química
Proteínas do Tecido Nervoso/metabolismo
Oxazóis/química
Oxazóis/farmacologia
Transferases (Outros Grupos de Fosfato Substituídos)/química
Transferases (Outros Grupos de Fosfato Substituídos)/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Membrane Proteins); 0 (Nerve Tissue Proteins); 0 (Oxazoles); 0 (Pyridines); EC 2.7.8.- (SGMS1 protein, human); EC 2.7.8.- (Transferases (Other Substituted Phosphate Groups))
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171125
[Lr] Data última revisão:
171125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170617
[St] Status:MEDLINE


  6 / 1252 MEDLINE  
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[PMID]:28522594
[Au] Autor:Ohnishi T; Hashizume C; Taniguchi M; Furumoto H; Han J; Gao R; Kinami S; Kosaka T; Okazaki T
[Ad] Endereço:Division of General and Digestive Surgery, Department of Medicine, Kanazawa Medical University, Uchinada, Japan.
[Ti] Título:Sphingomyelin synthase 2 deficiency inhibits the induction of murine colitis-associated colon cancer.
[So] Source:FASEB J;31(9):3816-3830, 2017 Sep.
[Is] ISSN:1530-6860
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Sphingomyelin synthase 2 (SMS2) is the synthetic enzyme of sphingomyelin (SM), which regulates membrane fluidity and microdomain structure. SMS2 plays a role in LPS-induced lung injury and inflammation; however, its role in inflammation-mediated tumorigenesis is unclear. We investigated the effect of SMS2 deficiency on dextran sodium sulfate (DSS)-induced murine colitis and found inhibition of DSS-induced inflammation in SMS2-deficient (SMS2 ) mice. DSS treatment induced a significant increase in ceramide levels, with a decrease of SM levels in SMS2 colon tissue, and demonstrated attenuation of the elevation of both inflammation-related gene expression and proinflammatory cytokines and chemokines, leukocyte infiltration, and MAPK and signal transducer and activator of transcription 3 activation. After undergoing transplantation of wild-type bone marrow, SMS2 mice also exhibited inhibition of DSS-induced inflammation in the colon, which suggested that SMS2 deficiency in bone marrow-derived immune cells was not involved in the inhibition of colitis. Finally, in an azoxymethane/DSS-induced cancer model, SMS2 deficiency significantly decreased tumor incidence in the colon. Our results demonstrate that SMS2 deficiency inhibits DSS-induced colitis and subsequent colitis-associated colon cancer inhibition of colon epithelial cell-mediated inflammation; therefore, inhibition of SMS2 may be a potential therapeutic target for human colitis and colorectal cancer.-Ohnishi, T., Hashizume, C., Taniguchi, M., Furumoto, H., Han, J., Gao, R., Kinami, S., Kosaka, T., Okazaki, T. Sphingomyelin synthase 2 deficiency inhibits the induction of murine colitis-associated colon cancer.
[Mh] Termos MeSH primário: Colite/complicações
Neoplasias do Colo/etiologia
Regulação Enzimológica da Expressão Gênica/fisiologia
Regulação Neoplásica da Expressão Gênica/fisiologia
Transferases (Outros Grupos de Fosfato Substituídos)/metabolismo
[Mh] Termos MeSH secundário: Animais
Proliferação Celular
Ceramidas/genética
Ceramidas/metabolismo
Colite/enzimologia
Neoplasias do Colo/enzimologia
Inflamação/metabolismo
Lipopolissacarídeos
Camundongos
Camundongos Knockout
Transdução de Sinais
Transferases (Outros Grupos de Fosfato Substituídos)/deficiência
Transferases (Outros Grupos de Fosfato Substituídos)/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ceramides); 0 (Lipopolysaccharides); EC 2.7.8.- (Transferases (Other Substituted Phosphate Groups)); EC 2.7.8.27 (sphingomyelin synthase 2, mouse)
[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:170520
[St] Status:MEDLINE
[do] DOI:10.1096/fj.201601225RR


  7 / 1252 MEDLINE  
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[PMID]:28505533
[Au] Autor:Adachi R; Ogawa K; Matsumoto SI; Satou T; Tanaka Y; Sakamoto J; Nakahata T; Okamoto R; Kamaura M; Kawamoto T
[Ad] Endereço:Biomolecular Research Laboratories, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan. Electronic address: ryutaro_adachi@hotmail.com.
[Ti] Título:Discovery and characterization of selective human sphingomyelin synthase 2 inhibitors.
[So] Source:Eur J Med Chem;136:283-293, 2017 Aug 18.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Sphingomyelin synthase (SMS) is a membrane enzyme that catalyzes the synthesis of sphingomyelin, is required for the maintenance of plasma membrane microdomain fluidity, and has two isoforms: SMS1 and SMS2. Although these isoforms exhibit the same SMS activity, they are different enzymes with distinguishable subcellular localizations. It was reported that SMS2 KO mice displayed lower inflammatory responses and anti-atherosclerotic effects, suggesting that inhibition of SMS2 would be a potential therapeutic approach for controlling inflammatory responses and atherosclerosis. This study aimed to discover a novel small-molecule compound that selectively inhibits SMS2 enzymatic activity. We developed a human SMS2 enzyme assay with a high-throughput mass spectrometry-based screening system. We characterized the enzymatic properties of SMS2 and established a high-throughput screening-compatible assay condition. To identify human SMS2 inhibitors, we conducted compound screening using the enzyme assay. We identified a 2-quinolone derivative as a SMS2 selective inhibitor with an IC of 950 nM and >100-fold selectivity for SMS2 over SMS1. The 2-quinolone exhibited efficacy in a cell-based engagement assay. We demonstrated that a more potent derivative directly bound to SMS2-expressing membrane fractions in an affinity selection mass spectrometry assay. Mutational analyses revealed that the interaction of the inhibitor with SMS2 required the presence of the amino acids S227 and H229, which are located in the catalytic domain of SMS2. In conclusion, we discovered novel SMS2-selective inhibitors. 2-Quinolone SMS2 inhibitors are considered applicable for leading optimization studies. Further investigations using these SMS2 inhibitors would provide validation tools for SMS2-relevant pathways in vitro and in vivo.
[Mh] Termos MeSH primário: Descoberta de Drogas
Inibidores Enzimáticos/farmacologia
Proteínas de Membrana/antagonistas & inibidores
Proteínas do Tecido Nervoso/antagonistas & inibidores
Bibliotecas de Moléculas Pequenas/farmacologia
Transferases (Outros Grupos de Fosfato Substituídos)/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Relação Dose-Resposta a Droga
Inibidores Enzimáticos/síntese química
Inibidores Enzimáticos/química
Células HEK293
Ensaios de Triagem em Larga Escala
Seres Humanos
Espectrometria de Massas
Proteínas de Membrana/deficiência
Proteínas de Membrana/metabolismo
Camundongos
Camundongos Knockout
Estrutura Molecular
Proteínas do Tecido Nervoso/deficiência
Proteínas do Tecido Nervoso/metabolismo
Bibliotecas de Moléculas Pequenas/síntese química
Bibliotecas de Moléculas Pequenas/química
Relação Estrutura-Atividade
Transferases (Outros Grupos de Fosfato Substituídos)/deficiência
Transferases (Outros Grupos de Fosfato Substituídos)/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Membrane Proteins); 0 (Nerve Tissue Proteins); 0 (Small Molecule Libraries); EC 2.7.8.- (SGMS1 protein, human); EC 2.7.8.- (Transferases (Other Substituted Phosphate Groups))
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170516
[St] Status:MEDLINE


  8 / 1252 MEDLINE  
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[PMID]:28411172
[Au] Autor:Piotto S; Sessa L; Iannelli P; Concilio S
[Ad] Endereço:Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, SA, Italy. Electronic address: piotto@unisa.it.
[Ti] Título:Computational study on human sphingomyelin synthase 1 (hSMS1).
[So] Source:Biochim Biophys Acta;1859(9 Pt B):1517-1525, 2017 09.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Human sphingomyelin synthase 1 (hSMS1) is the last enzyme for sphingomyelin (SM) biosynthesis. It has been discovered that in different human tumor tissues the SM levels are lower compared to normal tissues and the activation of hSMS1, to restore the normal levels of SM, inhibits cell cycle proliferation of cancer cells. Since the importance of SM and other lipid metabolism genes in the malignant transformation, we decided to explore the hSMS1 mechanism of action. Enzymes capable to regulate the formation of lipids are therefore of paramount importance. Here we present a computational study on sphingomyelin synthases hSMS1. The full structure of the enzyme was obtained by means of homology and ab initio techniques. Further molecular dynamics and docking studies permitted to identify putative binding sites and to identify the key residues for binding. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.
[Mh] Termos MeSH primário: Proteínas de Membrana/química
Proteínas do Tecido Nervoso/química
Transferases (Outros Grupos de Fosfato Substituídos)/química
[Mh] Termos MeSH secundário: Sítios de Ligação
Seres Humanos
Proteínas de Membrana/fisiologia
Simulação de Acoplamento Molecular
Simulação de Dinâmica Molecular
Proteínas do Tecido Nervoso/fisiologia
Transferases (Outros Grupos de Fosfato Substituídos)/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Membrane Proteins); 0 (Nerve Tissue Proteins); EC 2.7.8.- (SGMS1 protein, human); EC 2.7.8.- (Transferases (Other Substituted Phosphate Groups))
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170416
[St] Status:MEDLINE


  9 / 1252 MEDLINE  
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[PMID]:28352998
[Au] Autor:Xie Z; Zhang Z; Cao Z; Chen M; Li P; Liu W; Qin H; Zhao X; Tao Y; Chen Y
[Ad] Endereço:State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
[Ti] Título:An external substrate-free blue/white screening system in Escherichia coli.
[So] Source:Appl Microbiol Biotechnol;101(9):3811-3820, 2017 May.
[Is] ISSN:1432-0614
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Since the lacZα-based blue/white screening system was introduced to molecular biology, several different visual reporter systems were developed and used for various purposes in Escherichia coli. A common limit to the existent visual reporter systems is that an extracellular chromogenic substrate has to be added for the visible pigment production. In this study, we developed a new blue/white screening system based on a non-ribosomal peptide synthetase encoded by idgS from Streptomyces and a phosphopantetheinyl transferase encoded by sfp from Bacillus. When IdgS is activated from an apo-form to a holo-form via a posttranslational modification catalyzed by Sfp, it can synthesize a blue pigment indigoidine using L-glutamine, the amino acid abundant in cells, as a substrate. The new blue/white screening system contains a recipient E. coli strain with an optimized idgS gene cassette and a cloning vector harboring an sfp gene with an in-frame insertion of a multiple cloning site close to its N-terminal. We demonstrated that the IdgS/Sfp-based blue/white screening system is a powerful alternative to the lacZα-based screening system, which does not require any external substrate addition.
[Mh] Termos MeSH primário: Clonagem Molecular
Escherichia coli/genética
Testes Genéticos/métodos
Vetores Genéticos
Genética Microbiana/métodos
Biologia Molecular/métodos
Pigmentos Biológicos/análise
[Mh] Termos MeSH secundário: Bacillus/enzimologia
Bacillus/genética
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Cor
Peptídeo Sintases/genética
Peptídeo Sintases/metabolismo
Streptomyces/enzimologia
Streptomyces/genética
Transferases (Outros Grupos de Fosfato Substituídos)/genética
Transferases (Outros Grupos de Fosfato Substituídos)/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Pigments, Biological); 0 (phosphopantetheinyl transferase); EC 2.7.8.- (Transferases (Other Substituted Phosphate Groups)); EC 6.3.2.- (Peptide Synthases); EC 6.3.2.- (non-ribosomal peptide synthase)
[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:170330
[St] Status:MEDLINE
[do] DOI:10.1007/s00253-017-8252-2


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[PMID]:28284722
[Au] Autor:Carranza G; Angius F; Ilioaia O; Solgadi A; Miroux B; Arechaga I
[Ad] Endereço:Departamento de Biología Molecular and Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Universidad de Cantabria - CSIC - SODERCAN, Santander, Spain.
[Ti] Título:Cardiolipin plays an essential role in the formation of intracellular membranes in Escherichia coli.
[So] Source:Biochim Biophys Acta;1859(6):1124-1132, 2017 06.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Mitochondria, chloroplasts and photosynthetic bacteria are characterized by the presence of complex and intricate membrane systems. In contrast, non-photosynthetic bacteria lack membrane structures within their cytoplasm. However, large scale over-production of some membrane proteins, such as the fumarate reductase, the mannitol permease MtlA, the glycerol acyl transferase PlsB, the chemotaxis receptor Tsr or the ATP synthase subunit b, can induce the proliferation of intra cellular membranes (ICMs) in the cytoplasm of Escherichia coli. These ICMs are particularly rich in cardiolipin (CL). Here, we have studied the effect of CL in the generation of these membranous structures. We have deleted the three genes (clsA, clsB and clsC) responsible of CL biosynthesis in E. coli and analysed the effect of these mutations by fluorescent and electron microscopy and by lipid mass spectrometry. We have found that CL is essential in the formation of non-lamellar structures in the cytoplasm of E. coli cells. These results could help to understand the structuration of membranes in E. coli and other membrane organelles, such as mitochondria and ER.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Cardiolipinas/metabolismo
Retículo Endoplasmático/metabolismo
Escherichia coli/metabolismo
Proteínas de Membrana/deficiência
Mitocôndrias/metabolismo
Transferases (Outros Grupos de Fosfato Substituídos)/deficiência
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
ATPases Bacterianas Próton-Translocadoras/genética
ATPases Bacterianas Próton-Translocadoras/metabolismo
Retículo Endoplasmático/ultraestrutura
Escherichia coli/ultraestrutura
Corantes Fluorescentes/química
Deleção de Genes
Expressão Gênica
Isoenzimas/deficiência
Isoenzimas/genética
Proteínas de Membrana/genética
Mitocôndrias/ultraestrutura
Imagem com Lapso de Tempo
Transferases (Outros Grupos de Fosfato Substituídos)/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Cardiolipins); 0 (Fluorescent Dyes); 0 (Isoenzymes); 0 (Membrane Proteins); EC 2.7.8.- (Transferases (Other Substituted Phosphate Groups)); EC 2.7.8.- (cardiolipin synthetase); EC 3.6.1.- (Bacterial Proton-Translocating ATPases)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170629
[Lr] Data última revisão:
170629
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170313
[St] Status:MEDLINE



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