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[PMID]: 29351296 [Au] Autor: Passera A; Marcolungo L; Casati P; Brasca M; Quaglino F; Cantaloni C; Delledonne M [Ad] Endereço: Department of Agricultural and Environmental Sciences - Production, Landscape, Agroenergy, Università degli Studi di Milano, Milan, Italy. [Ti] Título: Hybrid genome assembly and annotation of Paenibacillus pasadenensis strain R16 reveals insights on endophytic life style and antifungal activity. [So] Source: PLoS One;13(1):e0189993, 2018. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Bacteria of the Paenibacillus genus are becoming important in many fields of science, including agriculture, for their positive effects on the health of plants. However, there are little information available on this genus compared to other bacteria (such as Bacillus or Pseudomonas), especially when considering genomic information. Sequencing the genomes of plant-beneficial bacteria is a crucial step to identify the genetic elements underlying the adaptation to life inside a plant host and, in particular, which of these features determine the differences between a helpful microorganism and a pathogenic one. In this study, we have characterized the genome of Paenibacillus pasadenensis, strain R16, recently investigated for its antifungal activities and plant-associated features. An hybrid assembly approach was used integrating the very precise reads obtained by Illumina technology and long fragments acquired with Oxford Nanopore Technology (ONT) sequencing. De novo genome assembly based solely on Illumina reads generated a relatively fragmented assembly of 5.72 Mbp in 99 ungapped sequences with an N50 length of 544 Kbp; hybrid assembly, integrating Illumina and ONT reads, improved the assembly quality, generating a genome of 5.75 Mbp, organized in 6 contigs with an N50 length of 3.4 Mbp. Annotation of the latter genome identified 4987 coding sequences, of which 1610 are hypothetical proteins. Enrichment analysis identified pathways of particular interest for the endophyte biology, including the chitin-utilization pathway and the incomplete siderophore pathway which hints at siderophore parasitism. In addition the analysis led to the identification of genes for the production of terpenes, as for example farnesol, that was hypothesized as the main antifungal molecule produced by the strain. The functional analysis on the genome confirmed several plant-associated, plant-growth promotion, and biocontrol traits of strain R16, thus adding insights in the genetic bases of these complex features, and of the Paenibacillus genus in general. [Mh] Termos MeSH primário: Endófitos/genética Fungos/patogenicidade Genoma Bacteriano Paenibacillus/genética Plantas/microbiologia [Mh] Termos MeSH secundário: Amino Açúcares/metabolismo Metabolismo dos Carboidratos DNA Bacteriano/genética DNA Bacteriano/isolamento & purificação Endófitos/metabolismo Endófitos/fisiologia Sequenciamento de Nucleotídeos em Larga Escala Compostos Orgânicos/metabolismo Paenibacillus/metabolismo Paenibacillus/fisiologia Desenvolvimento Vegetal Sideróforos/biossíntese Esporos Bacterianos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Amino Sugars); 0 (DNA, Bacterial); 0 (Organic Chemicals); 0 (Siderophores) [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: 180120 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0189993

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[PMID]: 29267289 [Au] Autor: Chen Y; Bieber MM; Bhat NM; Teng NNH [Ad] Endereço: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Stanford University, Stanford, California, United States of America. [Ti] Título: Ovarian carcinoma glyco-antigen targeted by human IgM antibody. [So] Source: PLoS One;12(12):e0187222, 2017. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Epithelial Ovarian Cancer (EOC) cells expression of a novel carbohydrate antigen was defined using a human VH4-34 encoded IgM monoclonal antibody (mAb216). MAb216 binds to a poly N-acetyllactosamine epitope expressed on B cells and kills normal and malignant B cells in vitro and in vivo. EOC patient ascites and EOC cell lines were used to study the anti tumor effect of mAb216. Various assays were used to characterize the epitope and demonstrate antibody-mediated binding and cytotoxicity in EOC. Drug and antibody combination effects were determined by calculating the combination index values using the Chou and Talalay method. MAb216 displays direct antibody mediated cytotoxicity on a population of human EOC tumor and ascites samples and EOC cell lines, which express high amounts of poly N-acetyllactosamine epitope, carried by CD147/CD98. Eighty four percent of patient samples, including platin resistant, had a tumor population that bound the monoclonal antibody. The binding pattern of mAb216 and mechanism of cytotoxicity was similar to that seen on normal and malignant B cells with unique general membrane disruption and "pore" formation. In vitro incubation with mAb216 and cisplatin enhanced killing of OVCAR3 cell line. In EOC cell lines percent cytotoxicity correlated with percent expression of epitope. Although in vitro data shows specific EOC cytotoxicity, for possible treatment of EOC MAb216 would need to be evaluated in a clinical trial with or without chemotherapy. [Mh] Termos MeSH primário: Anticorpos Monoclonais/imunologia Antígenos de Neoplasias/imunologia Imunoglobulina M/imunologia Neoplasias Epiteliais e Glandulares/imunologia Neoplasias Ovarianas/imunologia [Mh] Termos MeSH secundário: Amino Açúcares/imunologia Ascite/imunologia Linhagem Celular Tumoral Feminino Seres Humanos Microscopia Eletrônica de Varredura [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Amino Sugars); 0 (Antibodies, Monoclonal); 0 (Antigens, Neoplasm); 0 (Immunoglobulin M); 3Y5B2K5OOK (N-acetyllactosamine) [Em] Mês de entrada: 1801 [Cu] Atualização por classe: 180116 [Lr] Data última revisão: 180116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171222 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0187222

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[PMID]: 28977623 [Au] Autor: Gonzalez GM; Durica-Mitic S; Hardwick SW; Moncrieffe MC; Resch M; Neumann P; Ficner R; Görke B; Luisi BF [Ad] Endereço: Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK. [Ti] Título: Structural insights into RapZ-mediated regulation of bacterial amino-sugar metabolism. [So] Source: Nucleic Acids Res;45(18):10845-10860, 2017 Oct 13. [Is] ISSN: 1362-4962 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: In phylogenetically diverse bacteria, the conserved protein RapZ plays a central role in RNA-mediated regulation of amino-sugar metabolism. RapZ contributes to the control of glucosamine phosphate biogenesis by selectively presenting the regulatory small RNA GlmZ to the essential ribonuclease RNase E for inactivation. Here, we report the crystal structures of full length Escherichia coli RapZ at 3.40 Å and 3.25 Å, and its isolated C-terminal domain at 1.17 Å resolution. The structural data confirm that the N-terminal domain of RapZ possesses a kinase fold, whereas the C-terminal domain bears closest homology to a subdomain of 6-phosphofructokinase, an important enzyme in the glycolytic pathway. RapZ self-associates into a domain swapped dimer of dimers, and in vivo data support the importance of quaternary structure in RNA-mediated regulation of target gene expression. Based on biochemical, structural and genetic data, we suggest a mechanism for binding and presentation by RapZ of GlmZ and the closely related decoy sRNA, GlmY. We discuss a scenario for the molecular evolution of RapZ through re-purpose of enzyme components from central metabolism. [Mh] Termos MeSH primário: Proteínas de Escherichia coli/química Proteínas de Ligação a RNA/química [Mh] Termos MeSH secundário: Amino Açúcares/metabolismo Endorribonucleases/metabolismo Escherichia coli/metabolismo Proteínas de Escherichia coli/genética Proteínas de Escherichia coli/metabolismo Modelos Moleculares Mutação Ligação Proteica Domínios Proteicos Multimerização Proteica RNA/metabolismo Pequeno RNA não Traduzido/metabolismo Proteínas de Ligação a RNA/genética Proteínas de Ligação a RNA/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Amino Sugars); 0 (Escherichia coli Proteins); 0 (RNA, Small Untranslated); 0 (RNA-Binding Proteins); 0 (YhbJ protein, E coli); 63231-63-0 (RNA); EC 3.1.- (Endoribonucleases); EC 3.1.4.- (ribonuclease E) [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: 171005 [St] Status: MEDLINE [do] DOI: 10.1093/nar/gkx732

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[PMID]: 28621641 [Au] Autor: Chung ES; Lee JY; Rhee JY; Ko KS [Ad] Endereço: 1​Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea. [Ti] Título: Colistin resistance in Pseudomonas aeruginosa that is not linked to arnB. [So] Source: J Med Microbiol;66(6):833-841, 2017 Jun. [Is] ISSN: 1473-5644 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: PURPOSE: It is known that the arnB (or pmrH) gene encoding uridine 5'-(beta-1-threo-pentapyranosyl-4-ulose diphosphate) aminotransferase plays a critical role in colistin resistance in Pseudomonas aeruginosa through the addition of 4-amino-4-deoxy-l-arabinose (l-Ara4N) to lipid A. In this study, we attempted to obtain a colistin-resistant mutant from an arnB-deleted mutant through exposure to colistin. METHODOLOGY: We constructed an arnB deletion mutant (P5ΔarnB :: nptIII) from a colistin-susceptible strain (P5) by allelic replacement mutagenesis, and colistin-resistant mutants were selected in vitro using P5 and P5ΔarnB :: nptIII. The growth rate, lipid A structure, biofilm-forming activity and cell viability in diverse stressful conditions (osmotic, oxidative, acidic and heat stress) were investigated. Expression of phoP, pmrA, parR, and cprR was evaluated by qRT-PCR. RESULTS: An arnB deletion mutant was shown to develop colistin resistance through the addition of l-Ara4N to lipid A, despite a low survival rate (over 1000-fold lower than that of the wild-type strain) in the media with colistin. Two colistin-resistant mutants showed higher survival rates than colistin-susceptible strains against 5 % NaCl. In the presence of acidic and heat stress, P5ΔarnB :: nptIII-CstR exhibited higher survival rates during conditions of 1 % HCl and 42 °C than the other strains. Both phoP and pmrA genes were overexpressed significantly in both colistin-resistant mutants, but parR and cprR genes were not. CONCLUSION: We revealed that colistin resistance could be developed despite arnB deletion in P. aeruginosa through the addition of l-Ara4N to lipid A, which was accompanied by diverse physiological changes. [Mh] Termos MeSH primário: Antibacterianos/farmacologia Proteínas de Bactérias/genética Colistina/farmacologia Farmacorresistência Bacteriana Pseudomonas aeruginosa/efeitos dos fármacos Pseudomonas aeruginosa/genética [Mh] Termos MeSH secundário: Amino Açúcares/farmacologia Farmacorresistência Bacteriana/genética Genes Bacterianos Lipídeo A/metabolismo Testes de Sensibilidade Microbiana Viabilidade Microbiana/efeitos dos fármacos Mutação Estresse Fisiológico [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Amino Sugars); 0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (Lipid A); 0 (pmrA protein, Bacteria); 125360-99-8 (PhoP protein, Bacteria); 33406-49-4 (4-amino-4-deoxyarabinose); Z67X93HJG1 (Colistin) [Em] Mês de entrada: 1707 [Cu] Atualização por classe: 170726 [Lr] Data última revisão: 170726 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170617 [St] Status: MEDLINE [do] DOI: 10.1099/jmm.0.000456

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[PMID]: 28554839 [Au] Autor: Atmanene C; Ronin C; Téletchéa S; Gautier FM; Djedaïni-Pilard F; Ciesielski F; Vivat V; Grandjean C [Ad] Endereço: NovAliX Structural Biology Bioparc, Bd Sébastien Brant, BP30170, F-67405 Illkirch Cedex, France. [Ti] Título: Biophysical and structural characterization of mono/di-arylated lactosamine derivatives interaction with human galectin-3. [So] Source: Biochem Biophys Res Commun;489(3):281-286, 2017 Jul 29. [Is] ISSN: 1090-2104 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Combination of biophysical and structural techniques allowed characterizing and uncovering the mechanisms underlying increased binding affinity of lactosamine derivatives for galectin 3. In particular, complementing information gathered from X-ray crystallography, native mass spectrometry and isothermal microcalorimetry showed favorable enthalpic contribution of cation-π interaction between lactosamine aryl substitutions and arginine residues from the carbohydrate recognition domain, which resulted in two log increase in compound binding affinity. This incrementing strategy allowed individual contribution of galectin inhibitor moieties to be dissected. Altogether, our results suggest that core and substituents of these saccharide-based inhibitors can be optimized separately, providing valuable tools to study the role of galectins in diseases. [Mh] Termos MeSH primário: Amino Açúcares/química Amino Açúcares/farmacologia Galectina 3/metabolismo [Mh] Termos MeSH secundário: Calorimetria Cristalografia por Raios X Galectina 3/biossíntese Galectina 3/química Galectina 3/isolamento & purificação Seres Humanos Espectrometria de Massas Modelos Moleculares Conformação Molecular Relação Estrutura-Atividade [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Amino Sugars); 0 (Galectin 3); 0 (galectin-3, human); 13000-25-4 (lactosamine) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170925 [Lr] Data última revisão: 170925 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170531 [St] Status: MEDLINE

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[PMID]: 28374933 [Au] Autor: Abeln M; Borst KM; Cajic S; Thiesler H; Kats E; Albers I; Kuhn M; Kaever V; Rapp E; Münster-Kühnel A; Weinhold B [Ad] Endereço: Institute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany. [Ti] Título: Sialylation Is Dispensable for Early Murine Embryonic Development in Vitro. [So] Source: Chembiochem;18(13):1305-1316, 2017 Jul 04. [Is] ISSN: 1439-7633 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: The negatively charged nonulose sialic acid (Sia) is essential for murine development in vivo. In order to elucidate the impact of sialylation on differentiation processes in the absence of maternal influences, we generated mouse embryonic stem cell (mESC) lines that lack CMP-Sia synthetase (CMAS) and thereby the ability to activate Sia to CMP-Sia. Loss of CMAS activity resulted in an asialo cell surface accompanied by an increase in glycoconjugates with terminal galactosyl and oligo-LacNAc residues, as well as intracellular accumulation of free Sia. Remarkably, these changes did not impact intracellular metabolites or the morphology and transcriptome of pluripotent mESC lines. Moreover, the capacity of Cmas mESCs for undirected differentiation into embryoid bodies, germ layer formation and even the generation of beating cardiomyocytes provides first and conclusive evidence that pluripotency and differentiation of mESC in vitro can proceed in the absence of (poly)sialoglycans. [Mh] Termos MeSH primário: Camadas Germinativas/metabolismo Células-Tronco Embrionárias Murinas/metabolismo Miócitos Cardíacos/metabolismo N-Acilneuraminato Citidililtransferase/deficiência Células-Tronco Pluripotentes/metabolismo Ácidos Siálicos/metabolismo [Mh] Termos MeSH secundário: Amino Açúcares/metabolismo Animais Diferenciação Celular Linhagem Celular Embrião de Mamíferos Corpos Embrioides/citologia Corpos Embrioides/metabolismo Efeito Fundador Galactose/metabolismo Expressão Gênica Camadas Germinativas/citologia Glicoconjugados/metabolismo Células HEK293 Seres Humanos Camundongos Camundongos Endogâmicos C57BL Camundongos Transgênicos Células-Tronco Embrionárias Murinas/citologia Miócitos Cardíacos/citologia N-Acilneuraminato Citidililtransferase/genética Células-Tronco Pluripotentes/citologia Transcriptoma [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Amino Sugars); 0 (Glycoconjugates); 0 (Sialic Acids); 3Y5B2K5OOK (N-acetyllactosamine); EC 2.7.7.43 (N-Acylneuraminate Cytidylyltransferase); X2RN3Q8DNE (Galactose) [Em] Mês de entrada: 1707 [Cu] Atualização por classe: 170725 [Lr] Data última revisão: 170725 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170405 [St] Status: MEDLINE [do] DOI: 10.1002/cbic.201700083

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[PMID]: 28182413 [Au] Autor: De Schutter JW; Morrison JP; Morrison MJ; Ciulli A; Imperiali B [Ad] Endereço: Department of Chemistry, Massachusetts Institute of Technology , 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States. [Ti] Título: Targeting Bacillosamine Biosynthesis in Bacterial Pathogens: Development of Inhibitors to a Bacterial Amino-Sugar Acetyltransferase from Campylobacter jejuni. [So] Source: J Med Chem;60(5):2099-2118, 2017 Mar 09. [Is] ISSN: 1520-4804 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: The glycoproteins of selected microbial pathogens often include highly modified carbohydrates such as 2,4-diacetamidobacillosamine (diNAcBac). These glycoconjugates are involved in host-cell interactions and may be associated with the virulence of medically significant Gram-negative bacteria. In light of genetic studies demonstrating the attenuated virulence of bacterial strains in which modified carbohydrate biosynthesis enzymes have been knocked out, we are developing small molecule inhibitors of selected enzymes as tools to evaluate whether such compounds modulate virulence. We performed fragment-based and high-throughput screens against an amino-sugar acetyltransferase enzyme, PglD, involved in biosynthesis of UDP-diNAcBac in Campylobacter jejuni. Herein we report optimization of the hits into potent small molecule inhibitors (IC < 300 nM). Biophysical characterization shows that the best inhibitors are competitive with acetyl coenzyme A and an X-ray cocrystal structure reveals that binding is biased toward occupation of the adenine subpocket of the AcCoA binding site by an aromatic ring. [Mh] Termos MeSH primário: Acetiltransferases/antagonistas & inibidores Amino Açúcares/farmacologia Campylobacter jejuni/efeitos dos fármacos Hexosaminas/antagonistas & inibidores [Mh] Termos MeSH secundário: Campylobacter jejuni/enzimologia Campylobacter jejuni/metabolismo Hexosaminas/biossíntese [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Amino Sugars); 0 (Hexosamines); 7013-45-8 (4-deoxyneosamine C); EC 2.3.1.- (Acetyltransferases) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170922 [Lr] Data última revisão: 170922 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170210 [St] Status: MEDLINE [do] DOI: 10.1021/acs.jmedchem.6b01869

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[PMID]: 28167527 [Au] Autor: Choo M; Tan HL; Ding V; Castangia R; Belgacem O; Liau B; Hartley-Tassell L; Haslam SM; Dell A; Choo A [Ad] Endereço: From the Department of Life Sciences, Imperial College London, London SW7 2AZ, United Kingdom. [Ti] Título: Characterization of H type 1 and type 1 -acetyllactosamine glycan epitopes on ovarian cancer specifically recognized by the anti-glycan monoclonal antibody mAb-A4. [So] Source: J Biol Chem;292(15):6163-6176, 2017 Apr 14. [Is] ISSN: 1083-351X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Cancer-specific glycans of ovarian cancer are promising epitopes for targeting with monoclonal antibodies (mAb). Despite their potential, structural characterization of these glycan epitopes remains a significant challenge in mAb preclinical development. Our group generated the monoclonal antibody mAb-A4 against human embryonic stem cells (hESC), which also bound specifically to -glycans present on 11 of 19 ovarian cancer (OC) and 8 of 14 breast cancer cell lines tested. Normal cell lines and tissue were unstained by mAb-A4. To characterize the -linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). The mAb-A4 epitopes were found to be Fucα1-2Galß1-3GlcNAcß (H type 1) and Galß1-3GlcNAcß (type 1 LacNAc). These structures were found to be present on multiple proteins from hESC and OC. Importantly, endo-ß-galactosidase coupled with MALDI-MS allowed these two epitopes, for the first time, to be directly identified on the polylactosamines of -glycans of SKOV3, IGROV1, OV90, and OVCA433. Furthermore, siRNA knockdown of B3GALT5 expression in SKOV3 demonstrated that mAb-A4 binding was dependent on B3GALT5, providing orthogonal evidence of the epitopes' structures. The recognition of oncofetal H type 1 and type 1 LacNAc on OC by mAb-A4 is a novel and promising way to target OC and supports the theory that cancer can acquire stem-like phenotypes. We propose that the orthogonal framework used in this work could be the basis for advancing anti-glycan mAb characterization. [Mh] Termos MeSH primário: Amino Açúcares/imunologia Anticorpos Monoclonais Murinos/imunologia Anticorpos Antineoplásicos/imunologia Antígenos de Neoplasias/imunologia Epitopos/imunologia Células-Tronco Neoplásicas/imunologia Neoplasias Ovarianas/imunologia [Mh] Termos MeSH secundário: Neoplasias da Mama/imunologia Linhagem Celular Tumoral Feminino Seres Humanos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Amino Sugars); 0 (Antibodies, Monoclonal, Murine-Derived); 0 (Antibodies, Neoplasm); 0 (Antigens, Neoplasm); 0 (Epitopes); 3Y5B2K5OOK (N-acetyllactosamine) [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: 170208 [St] Status: MEDLINE [do] DOI: 10.1074/jbc.M116.768887

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[PMID]: 28166391 [Au] Autor: Dion J; Deshayes F; Storozhylova N; Advedissian T; Lambert A; Viguier M; Tellier C; Dussouy C; Poirier F; Grandjean C [Ad] Endereço: Faculté des Sciences et des Techniques, Unité Fonctionnalité et Ingénierie des Protéines (UFIP), Université de Nantes, UMR CNRS 6286, 2 chemin de la Houssinière, B. P. 92208, 44322, Nantes Cedex 3, France. [Ti] Título: Lactosamine-Based Derivatives as Tools to Delineate the Biological Functions of Galectins: Application to Skin Tissue Repair. [So] Source: Chembiochem;18(8):782-789, 2017 Apr 18. [Is] ISSN: 1439-7633 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: Galectins have been recognized as potential novel therapeutic targets for the numerous fundamental biological processes in which they are involved. Galectins are key players in homeostasis, and as such their expression and function are finely tuned in vivo. Thus, their modes of action are complex and remain largely unexplored, partly because of the lack of dedicated tools. We thus designed galectin inhibitors from a lactosamine core, functionalized at key C2 and C3' positions by aromatic substituents to ensure both high affinity and selectivity, and equipped with a spacer that can be modified on demand to further modulate their physico-chemical properties. As a proof-of-concept, galectin-3 was selectively targeted. The efficacy of the synthesized di-aromatic lactosamine tools was shown in cellular assays to modulate collective epithelial cell migration and to interfere with actin/cortactin localization. [Mh] Termos MeSH primário: Amino Açúcares/farmacologia Galectina 3/antagonistas & inibidores Cicatrização/efeitos dos fármacos [Mh] Termos MeSH secundário: Amino Açúcares/síntese química Amino Açúcares/química Linhagem Celular Movimento Celular/efeitos dos fármacos Polaridade Celular/efeitos dos fármacos Células Epiteliais/efeitos dos fármacos Células Epiteliais/fisiologia Galectina 1/antagonistas & inibidores Galectinas/antagonistas & inibidores Seres Humanos Queratinócitos/efeitos dos fármacos Queratinócitos/fisiologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Amino Sugars); 0 (Galectin 1); 0 (Galectin 3); 0 (Galectins); 0 (LGALS7 protein, human); 0 (galectin-3, human); 13000-25-4 (lactosamine) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170919 [Lr] Data última revisão: 170919 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170207 [St] Status: MEDLINE [do] DOI: 10.1002/cbic.201600673

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[PMID]: 27800627 [Au] Autor: Jorge JM; Nguyen AQ; Pérez-García F; Kind S; Wendisch VF [Ad] Endereço: Faculty of Biology and CeBiTec, Genetics of Prokaryotes, Bielefeld University, Universitätsstr. 25, Bielefeld 33615, Germany. [Ti] Título: Improved fermentative production of gamma-aminobutyric acid via the putrescine route: Systems metabolic engineering for production from glucose, amino sugars, and xylose. [So] Source: Biotechnol Bioeng;114(4):862-873, 2017 Apr. [Is] ISSN: 1097-0290 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Gamma-aminobutyric acid (GABA) is a non-protein amino acid widespread in Nature. Among the various uses of GABA, its lactam form 2-pyrrolidone can be chemically converted to the biodegradable plastic polyamide-4. In metabolism, GABA can be synthesized either by decarboxylation of l-glutamate or by a pathway that starts with the transamination of putrescine. Fermentative production of GABA from glucose by recombinant Corynebacterium glutamicum has been described via both routes. Putrescine-based GABA production was characterized by accumulation of by-products such as N-acetyl-putrescine. Their formation was abolished by deletion of the spermi(di)ne N-acetyl-transferase gene snaA. To improve provision of l-glutamate as precursor 2-oxoglutarate dehydrogenase activity was reduced by changing the translational start codon of the chromosomal gene for 2-oxoglutarate dehydrogenase subunit E1o to the less preferred TTG and by maintaining the inhibitory protein OdhI in its inhibitory form by changing amino acid residue 15 from threonine to alanine. Putrescine-based GABA production by the strains described here led to GABA titers up to 63.2 g L in fed-batch cultivation at maximum volumetric productivities up to 1.34 g L h , the highest volumetric productivity for fermentative GABA production reported to date. Moreover, GABA production from the carbon sources xylose, glucosamine, and N-acetyl-glucosamine that do not have competing uses in the food or feed industries was established. Biotechnol. Bioeng. 2017;114: 862-873. © 2016 Wiley Periodicals, Inc. [Mh] Termos MeSH primário: Engenharia Metabólica/métodos Putrescina/metabolismo Biologia de Sistemas/métodos Ácido gama-Aminobutírico/metabolismo [Mh] Termos MeSH secundário: Amino Açúcares Técnicas de Cultura Celular por Lotes Biomassa Corynebacterium glutamicum/metabolismo Fermentação Glucose/metabolismo Xilose/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Amino Sugars); 56-12-2 (gamma-Aminobutyric Acid); A1TA934AKO (Xylose); IY9XDZ35W2 (Glucose); V10TVZ52E4 (Putrescine) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171010 [Lr] Data última revisão: 171010 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161102 [St] Status: MEDLINE [do] DOI: 10.1002/bit.26211

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