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  1 / 1992 MEDLINE  
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[PMID]:29352301
[Au] Autor:Shah BS; Ashwood HE; Harrop SJ; Farrugia DN; Paulsen IT; Mabbutt BC
[Ad] Endereço:Department of Molecular Sciences, Macquarie University, Sydney, Australia.
[Ti] Título:Crystal structure of a UDP-GlcNAc epimerase for surface polysaccharide biosynthesis in Acinetobacter baumannii.
[So] Source:PLoS One;13(1):e0191610, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:With new strains of Acinetobacter baumannii undergoing genomic analysis, it has been possible to define regions of genomic plasticity (RGPs), encoding specific adaptive elements. For a selected RGP from a community-derived isolate of A. baumannii, we outline sequences compatible with biosynthetic machinery of surface polysaccharides, specifically enzymes utilized in the dehydration and conversion of UDP-N-acetyl-D-glucosamine (UDP-D-GlcNAc). We have determined the crystal structure of one of these, the epimerase Ab-WbjB. This dehydratase belongs to the 'extended' short-chain dehydrogenase/reductase (SDR) family, related in fold to previously characterised enzymes CapE and FlaA1. Our 2.65Å resolution structure of Ab-WbjB shows a hexamer, organised into a trimer of chain pairs, with coenzyme NADP+ occupying each chain. Specific active-site interactions between each coenzyme and a lysine quaternary group of a neighbouring chain interconnect adjacent dimers, so stabilising the hexameric form. We show UDP-GlcNAc to be a specific substrate for Ab-WbjB, with binding evident by ITC (Ka = 0.23 µmol-1). The sequence of Ab-WbjB shows variation from the consensus active-site motifs of many SDR enzymes, demonstrating a likely catalytic role for a specific threonine sidechain (as an alternative to tyrosine) in the canonical active site chemistry of these epimerases.
[Mh] Termos MeSH primário: Acinetobacter baumannii/enzimologia
Proteínas de Bactérias/química
Carboidratos Epimerases/química
[Mh] Termos MeSH secundário: Acinetobacter baumannii/genética
Acinetobacter baumannii/isolamento & purificação
Sequência de Aminoácidos
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Carboidratos Epimerases/genética
Carboidratos Epimerases/metabolismo
Domínio Catalítico
Cristalografia por Raios X
Seres Humanos
Modelos Moleculares
Polissacarídeos Bacterianos/biossíntese
Conformação Proteica
Domínios Proteicos
Estrutura Quaternária de Proteína
Homologia de Sequência de Aminoácidos
Eletricidade Estática
Homologia Estrutural de Proteína
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Polysaccharides, Bacterial); EC 5.1.3.- (Carbohydrate Epimerases)
[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:180121
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191610


  2 / 1992 MEDLINE  
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[PMID]:29199987
[Au] Autor:Shornikov A; Tran H; Macias J; Halavaty AS; Minasov G; Anderson WF; Kuhn ML
[Ad] Endereço:Department of Chemistry and Biochemistry, San Francisco State University, USA.
[Ti] Título:Structure of the Bacillus anthracis dTDP-L-rhamnose-biosynthetic enzyme dTDP-4-dehydrorhamnose 3,5-epimerase (RfbC).
[So] Source:Acta Crystallogr F Struct Biol Commun;73(Pt 12):664-671, 2017 Dec 01.
[Is] ISSN:2053-230X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The exosporium layer of Bacillus anthracis spores is rich in L-rhamnose, a common bacterial cell-wall component, which often contributes to the virulence of pathogens by increasing their adherence and immune evasion. The biosynthetic pathway used to form the activated L-rhamnose donor dTDP-L-rhamnose consists of four enzymes (RfbA, RfbB, RfbC and RfbD) and is an attractive drug target because there are no homologs in mammals. It was found that co-purifying and screening RfbC (dTDP-6-deoxy-D-xylo-4-hexulose 3,5-epimerase) from B. anthracis in the presence of the other three B. anthracis enzymes of the biosynthetic pathway yielded crystals that were suitable for data collection. RfbC crystallized as a dimer and its structure was determined at 1.63 Šresolution. Two different ligands were bound in the protein structure: pyrophosphate in the active site of one monomer and dTDP in the other monomer. A structural comparison with RfbC homologs showed that the key active-site residues are conserved across kingdoms.
[Mh] Termos MeSH primário: Bacillus anthracis/enzimologia
Proteínas de Bactérias/química
Carboidratos Epimerases/química
[Mh] Termos MeSH secundário: Proteínas de Bactérias/metabolismo
Carboidratos Epimerases/metabolismo
Domínio Catalítico
Cristalografia por Raios X
Difosfatos/química
Difosfatos/metabolismo
Modelos Moleculares
Conformação Proteica
Homologia Estrutural de Proteína
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Diphosphates); 4E862E7GRQ (diphosphoric acid); EC 5.1.3.- (Carbohydrate Epimerases); EC 5.1.3.13 (dTDP-4-ketorhamnose 3,5-epimerase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171205
[St] Status:MEDLINE
[do] DOI:10.1107/S2053230X17015849


  3 / 1992 MEDLINE  
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[PMID]:29371662
[Au] Autor:Bohl TE; Shi K; Lee JK; Aihara H
[Ad] Endereço:Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota Twin Cities, Minneapolis, MN, 55455, USA.
[Ti] Título:Crystal structure of lipid A disaccharide synthase LpxB from Escherichia coli.
[So] Source:Nat Commun;9(1):377, 2018 01 25.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Most Gram-negative bacteria are surrounded by a glycolipid called lipopolysaccharide (LPS), which forms a barrier to hydrophobic toxins and, in pathogenic bacteria, is a virulence factor. During LPS biosynthesis, a membrane-associated glycosyltransferase (LpxB) forms a tetra-acylated disaccharide that is further acylated to form the membrane anchor moiety of LPS. Here we solve the structure of a soluble and catalytically competent LpxB by X-ray crystallography. The structure reveals that LpxB has a glycosyltransferase-B family fold but with a highly intertwined, C-terminally swapped dimer comprising four domains. We identify key catalytic residues with a product, UDP, bound in the active site, as well as clusters of hydrophobic residues that likely mediate productive membrane association or capture of lipidic substrates. These studies provide the basis for rational design of antibiotics targeting a crucial step in LPS biosynthesis.
[Mh] Termos MeSH primário: Escherichia coli/enzimologia
Lipopolissacarídeos/química
N-Acetilglucosaminiltransferases/química
Difosfato de Uridina/química
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Carboidratos Epimerases/química
Carboidratos Epimerases/genética
Carboidratos Epimerases/metabolismo
Domínio Catalítico
Clonagem Molecular
Cristalografia por Raios X
Escherichia coli/genética
Expressão Gênica
Vetores Genéticos/química
Vetores Genéticos/metabolismo
Interações Hidrofóbicas e Hidrofílicas
Lipopolissacarídeos/biossíntese
Modelos Moleculares
N-Acetilglucosaminiltransferases/genética
N-Acetilglucosaminiltransferases/metabolismo
Ligação Proteica
Dobramento de Proteína
Domínios e Motivos de Interação entre Proteínas
Multimerização Proteica
Estrutura Secundária de Proteína
Homologia Estrutural de Proteína
Especificidade por Substrato
Thermus thermophilus/enzimologia
Thermus thermophilus/genética
Difosfato de Uridina/metabolismo
[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 (Lipopolysaccharides); 58-98-0 (Uridine Diphosphate); EC 2.4.1.- (N-Acetylglucosaminyltransferases); EC 2.4.1.182 (lipid A disaccharide synthase); EC 5.1.3.- (Carbohydrate Epimerases); EC 5.1.3.14 (UDP acetylglucosamine-2-epimerase)
[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:180127
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02712-9


  4 / 1992 MEDLINE  
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[PMID]:29241902
[Au] Autor:Olberg B; Fuchs S; Panteli D; Perleth M; Busse R
[Ad] Endereço:Berlin University of Technology, Germany; Federal Joint Committee, Berlin, Germany. Electronic address: britta.olberg@googlemail.com.
[Ti] Título:Scientific Evidence in Health Technology Assessment Reports: An In-Depth Analysis of European Assessments on High-Risk Medical Devices.
[So] Source:Value Health;20(10):1420-1426, 2017 12.
[Is] ISSN:1524-4733
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The aim of this study was to examine the scientific evidence on clinical effectiveness and safety used in health technology assessments (HTAs) of high-risk medical devices (MDs) in Europe. METHODS: We applied a systematic approach to identify European institutions involved in HTA and to select reports assessing MDs considered high-risk according to the definition in the new German health care regulation §137h. Reports published between 2010 and 2015 were considered in our subsequent analysis. We used a structured tool based on widely accepted methodologic principles from Drummond's framework to extract key information on the clinical evidence considered in the reports. RESULTS: Out of 1376 identified reports, 93 were eligible for analysis. All reports based their assessment primarily on direct evidence, in most cases (68%) identified through an independent systematic literature search. In more than half the identified studies considered in the reports, clinical evidence for demonstration of effectiveness and safety was of moderate or low quality. Even when systematic reviews and randomized controlled trials were available for assessment, most studies showed an unclear or high risk of bias. CONCLUSIONS: This study confirms that the quality of scientific evidence used in HTA of high-risk MDs is low and therefore the use of evidence needs improvement. The European Commission recently updated the regulation on MDs but mainly focused on the safety of materials and the CE (Conformité Européene [European Conformity]) mark. Our results show that additional changes are necessary, specifically with regard to the marketing authorization process of MDs, with stricter quality requirements based on methodologically robust trials, possibly in combination with other evidence sources.
[Mh] Termos MeSH primário: Segurança de Equipamentos
Equipamentos e Provisões
Avaliação da Tecnologia Biomédica/métodos
[Mh] Termos MeSH secundário: Proteínas de Arabidopsis
Carboidratos Epimerases
Equipamentos e Provisões/efeitos adversos
Europa (Continente)
Seres Humanos
Ensaios Clínicos Controlados Aleatórios como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Arabidopsis Proteins); EC 5.1.3.- (Carbohydrate Epimerases); EC 5.1.3.- (GER1 protein, Arabidopsis)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180202
[Lr] Data última revisão:
180202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE


  5 / 1992 MEDLINE  
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[PMID]:28899942
[Au] Autor:Ma M; Li de la Sierra-Gallay I; Lazar N; Pellegrini O; Lepault J; Condon C; Durand D; van Tilbeurgh H
[Ad] Endereço:Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS UMR 9198, Univ. Paris-Sud, Université Paris-Saclay, 91198 Gif sur Yvette Cedex, France.
[Ti] Título:Trz1, the long form RNase Z from yeast, forms a stable heterohexamer with endonuclease Nuc1 and mutarotase.
[So] Source:Biochem J;474(21):3599-3613, 2017 Oct 18.
[Is] ISSN:1470-8728
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Proteomic studies have established that Trz1, Nuc1 and mutarotase form a complex in yeast. Trz1 is a ß-lactamase-type RNase composed of two ß-lactamase-type domains connected by a long linker that is responsible for the endonucleolytic cleavage at the 3'-end of tRNAs during the maturation process (RNase Z activity); Nuc1 is a dimeric mitochondrial nuclease involved in apoptosis, while mutarotase (encoded by YMR099C) catalyzes the conversion between the α- and ß-configuration of glucose-6-phosphate. Using gel filtration, small angle X-ray scattering and electron microscopy, we demonstrated that Trz1, Nuc1 and mutarotase form a very stable heterohexamer, composed of two copies of each of the three subunits. A Nuc1 homodimer is at the center of the complex, creating a two-fold symmetry and interacting with both Trz1 and mutarotase. Enzymatic characterization of the ternary complex revealed that the activities of Trz1 and mutarotase are not affected by complex formation, but that the Nuc1 activity is completely inhibited by mutarotase and partially by Trz1. This suggests that mutarotase and Trz1 might be regulators of the Nuc1 apoptotic nuclease activity.
[Mh] Termos MeSH primário: Carboidratos Epimerases/química
Endonucleases/química
Endorribonucleases/química
Exonucleases/química
Proteínas de Saccharomyces cerevisiae/química
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Carboidratos Epimerases/genética
Endonucleases/genética
Endorribonucleases/genética
Exonucleases/genética
Estabilidade Proteica
Estrutura Secundária de Proteína
Proteínas de Saccharomyces cerevisiae/genética
Espalhamento a Baixo Ângulo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Saccharomyces cerevisiae Proteins); EC 3.1.- (Endonucleases); EC 3.1.- (Endoribonucleases); EC 3.1.- (Exonucleases); EC 3.1.- (Nuc1 protein, S cerevisiae); EC 3.1.- (RNase Z); EC 3.1.- (tRNase Z, S cerevisiae); EC 5.1.3.- (Carbohydrate Epimerases); EC 5.1.3.3 (aldose 1-epimerase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170914
[St] Status:MEDLINE
[do] DOI:10.1042/BCJ20170435


  6 / 1992 MEDLINE  
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[PMID]:28734894
[Au] Autor:Belyavskaya VA; Prudnikova TY; Domanitskaya NV; Litviakov NV; Maksimov VN; Cherdyntseva NV; Grigorieva EV
[Ad] Endereço:Research Center of Virology and Biotechnology, Vector, Koltsovo 630559, Novosibirsk region, Russia.
[Ti] Título:GLCE rs3865014 (Val597Ile) polymorphism is associated with breast cancer susceptibility and triple-negative breast cancer in Siberian population.
[So] Source:Gene;628:224-229, 2017 Sep 10.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:d-Glucuronyl C5-epimerase (GLCE) is one of key enzymes in heparan sulfate biosynthesis and possesses tumour-suppressor function in breast carcinogenesis. Here, we investigated a potential involvement of GLCE polymorphism(s) in breast cancer development in Siberian women population. Comprehensive analysis of SNP databases revealed GLCE rs3865014 (Val597Ile) missense polymorphism as the main significantly present in human populations. According the TaqMan-based SNP assay, allele distributions for the rs3865014 (A>G) were similar in healthy Siberian women (n=136) and cancer patients (n=129) (A0,73:G0,27) and intermediate between the European and Asian populations, while genotype distributions were different, with the increase of AG rate in breast cancer patients (OR=1.76; 95% CI=1.04-1.90; P(Y)=0.035 χ =4.44). Heterozygous AG genotype was associated with tumour size (OR=3.67, P(Y)=0.004), ER-negative tumours (OR=3.25, P(Y)=0.0028), triple-negative tumours (OR=4.94, P(Y)=0.015) but not menopausal status, PR and HER-2 status, local or distant metastasis. Homozygous GLCE genotypes (AA/GG) were more common for ER+PR+ luminal A breast cancer (OR=0.25, P(Y)=0.031). Loss-of-heterozigosity was identified in 5 of 51 breast tumours and the loss of G allele was associated with the decreased GLCE expression. Epidemiologic data for the GLCE SNP in different racial/ethnic groups demonstrated high AG genotype rates as a risk factor not for breast cancer incidence but for poor prognosis of the disease. The obtained data suggest an involvement of GLCE rs3865014 in breast cancer development. Heterozygous AG genotype might be a risk factor for breast cancer susceptibility in Siberian women and is associated with aggressive ER-negative and triple-negative cancer subtypes.
[Mh] Termos MeSH primário: Grupo com Ancestrais do Continente Asiático/genética
Neoplasias da Mama/genética
Carboidratos Epimerases/genética
Predisposição Genética para Doença
Polimorfismo de Nucleotídeo Único
Neoplasias de Mama Triplo Negativas/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Alelos
Substituição de Aminoácidos
Biomarcadores Tumorais
Neoplasias da Mama/epidemiologia
Neoplasias da Mama/patologia
Estudos de Casos e Controles
Códon
Grupo com Ancestrais do Continente Europeu/genética
Feminino
Expressão Gênica
Genótipo
Seres Humanos
Perda de Heterozigosidade
Metanálise como Assunto
Meia-Idade
Estadiamento de Neoplasias
Risco
Sibéria/epidemiologia
Neoplasias de Mama Triplo Negativas/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Codon); EC 5.1.3.- (Carbohydrate Epimerases); EC 5.1.3.17 (glucuronic acid epimerase, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170724
[St] Status:MEDLINE


  7 / 1992 MEDLINE  
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[PMID]:28594817
[Au] Autor:Maharjan RP; Ferenci T
[Ad] Endereço:School of Life and Environmental Sciences, University of Sydney, Sydney, New South Wales, Australia.
[Ti] Título:A shifting mutational landscape in 6 nutritional states: Stress-induced mutagenesis as a series of distinct stress input-mutation output relationships.
[So] Source:PLoS Biol;15(6):e2001477, 2017 Jun.
[Is] ISSN:1545-7885
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Environmental stresses increase genetic variation in bacteria, plants, and human cancer cells. The linkage between various environments and mutational outcomes has not been systematically investigated, however. Here, we established the influence of nutritional stresses commonly found in the biosphere (carbon, phosphate, nitrogen, oxygen, or iron limitation) on both the rate and spectrum of mutations in Escherichia coli. We found that each limitation was associated with a remarkably distinct mutational profile. Overall mutation rates were not always elevated, and nitrogen, iron, and oxygen limitation resulted in major spectral changes but no net increase in rate. Our results thus suggest that stress-induced mutagenesis is a diverse series of stress input-mutation output linkages that is distinct in every condition. Environment-specific spectra resulted in the differential emergence of traits needing particular mutations in these settings. Mutations requiring transpositions were highest under iron and oxygen limitation, whereas base-pair substitutions and indels were highest under phosphate limitation. The unexpected diversity of input-output effects explains some important phenomena in the mutational biases of evolving genomes. The prevalence of bacterial insertion sequence transpositions in the mammalian gut or in anaerobically stored cultures is due to environmentally determined mutation availability. Likewise, the much-discussed genomic bias towards transition base substitutions in evolving genomes can now be explained as an environment-specific output. Altogether, our conclusion is that environments influence genetic variation as well as selection.
[Mh] Termos MeSH primário: DNA Bacteriano
Escherichia coli K12/fisiologia
Interação Gene-Ambiente
Modelos Genéticos
Mutagênese
Mutação
Estresse Fisiológico
[Mh] Termos MeSH secundário: Carboidratos Epimerases/genética
Carboidratos Epimerases/metabolismo
Células Clonais
Análise por Conglomerados
DNA Bacteriano/metabolismo
Escherichia coli K12/genética
Escherichia coli K12/crescimento & desenvolvimento
Escherichia coli K12/isolamento & purificação
Proteínas de Escherichia coli/genética
Proteínas de Escherichia coli/metabolismo
Fermentação
Perfilação da Expressão Gênica
Regulação Bacteriana da Expressão Gênica
Mutação INDEL
Mutagênese Insercional
Taxa de Mutação
Mutação de Sentido Incorreto
Nutrigenômica/métodos
Mutação Puntual
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Bacterial); 0 (Escherichia coli Proteins); EC 5.1.3.- (Carbohydrate Epimerases); EC 5.1.3.4 (L-ribulosephosphate 4-epimerase)
[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:170609
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pbio.2001477


  8 / 1992 MEDLINE  
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[PMID]:28424265
[Au] Autor:Pham ND; Pang PC; Krishnamurthy S; Wands AM; Grassi P; Dell A; Haslam SM; Kohler JJ
[Ad] Endereço:From the Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9038 and.
[Ti] Título:Effects of altered sialic acid biosynthesis on -linked glycan branching and cell surface interactions.
[So] Source:J Biol Chem;292(23):9637-9651, 2017 Jun 09.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:GNE (UDP-GlcNAc 2-epimerase/ManNAc kinase) myopathy is a rare muscle disorder associated with aging and is related to sporadic inclusion body myositis, the most common acquired muscle disease of aging. Although the cause of sporadic inclusion body myositis is unknown, GNE myopathy is associated with mutations in GNE. GNE harbors two enzymatic activities required for biosynthesis of sialic acid in mammalian cells. Mutations to both GNE domains are linked to GNE myopathy. However, correlation between mutation-associated reductions in sialic acid production and disease severity is imperfect. To investigate other potential effects of GNE mutations, we compared sialic acid production in cell lines expressing wild type or mutant forms of GNE. Although we did not detect any differences attributable to disease-associated mutations, lectin binding and mass spectrometry analysis revealed that GNE deficiency is associated with unanticipated effects on the structure of cell-surface glycans. In addition to exhibiting low levels of sialylation, GNE-deficient cells produced distinct -linked glycan structures with increased branching and extended poly- -acetyllactosamine. GNE deficiency may affect levels of UDP-GlcNAc, a key metabolite in the nutrient-sensing hexosamine biosynthetic pathway, but this modest effect did not fully account for the change in -linked glycan structure. Furthermore, GNE deficiency and glucose supplementation acted independently and additively to increase -linked glycan branching. Notably, -linked glycans produced by GNE-deficient cells displayed enhanced binding to galectin-1, indicating that changes in GNE activity can alter affinity of cell-surface glycoproteins for the galectin lattice. These findings suggest an unanticipated mechanism by which GNE activity might affect signaling through cell-surface receptors.
[Mh] Termos MeSH primário: Acetilglucosamina/biossíntese
Membrana Celular/metabolismo
Polissacarídeos/biossíntese
Ácidos Siálicos/biossíntese
[Mh] Termos MeSH secundário: Acetilglucosamina/genética
Carboidratos Epimerases/genética
Carboidratos Epimerases/metabolismo
Linhagem Celular
Membrana Celular/genética
Seres Humanos
Mutação
Miosite de Corpos de Inclusão/genética
Miosite de Corpos de Inclusão/metabolismo
Polissacarídeos/genética
Domínios Proteicos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Polysaccharides); 0 (Sialic Acids); 0 (poly-N-acetyl glucosamine); EC 5.1.3.- (Carbohydrate Epimerases); EC 5.1.3.14 (UDP acetylglucosamine-2-epimerase); V956696549 (Acetylglucosamine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170618
[Lr] Data última revisão:
170618
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170421
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.764597


  9 / 1992 MEDLINE  
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[PMID]:28403215
[Au] Autor:Pardeshi P; Rao KK; Balaji PV
[Ad] Endereço:Department of Biosciences and Bioengineering Indian Institute of Technology Bombay Powai, Mumbai, India.
[Ti] Título:Rv3634c from Mycobacterium tuberculosis H37Rv encodes an enzyme with UDP-Gal/Glc and UDP-GalNAc 4-epimerase activities.
[So] Source:PLoS One;12(4):e0175193, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A bioinformatics study revealed that Mycobacterium tuberculosis H37Rv (Mtb) contains sequence homologs of Campylobacter jejuni protein glycosylation enzymes. The ORF Rv3634c from Mtb was identified as a sequence homolog of C. jejuni UDP-Gal/GalNAc 4-epimerase. This study reports the cloning of Rv3634c and its expression as an N-terminal His-tagged protein. The recombinant protein was shown to have UDP-Gal/Glc 4-epimerase activity by GOD-POD assay and by reverse phase HPLC. This enzyme was shown to have UDP-GalNAc 4-epimerase activity also. Residues Ser121, Tyr146 and Lys150 were shown by site-directed mutagenesis to be important for enzyme activity. Mutation of Ser121 and Tyr146 to Ala and Phe, respectively, led to complete loss of activity whereas mutation of Lys150 to Arg led to partial loss of activity. There were no gross changes in the secondary structures of any of these three mutants. These results suggest that Ser121 and Tyr146 are essential for epimerase activity of Rv3634c. UDP-Gal/Glc 4-epimerases from other organisms also have a catalytic triad consisting of Ser, Tyr and Lys. The triad carries out proton transfer from nucleotide sugar to NAD+ and back, thus effecting the epimerization of the substrate. Addition of NAD+ to Lys150 significantly abrogates the loss of activity, suggesting that, as in other epimerases, NAD+ is associated with Rv3634c.
[Mh] Termos MeSH primário: Carboidratos Epimerases/genética
Carboidratos Epimerases/metabolismo
Mycobacterium tuberculosis/enzimologia
Mycobacterium tuberculosis/genética
UDPglucose 4-Epimerase/genética
UDPglucose 4-Epimerase/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Campylobacter jejuni/química
Campylobacter jejuni/enzimologia
Campylobacter jejuni/genética
Campylobacter jejuni/metabolismo
Carboidratos Epimerases/química
Clonagem Molecular
Genômica
Seres Humanos
Mutagênese Sítio-Dirigida
Mycobacterium tuberculosis/química
Mycobacterium tuberculosis/metabolismo
Mutação Puntual
Conformação Proteica
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Alinhamento de Sequência
Tuberculose/microbiologia
UDPglucose 4-Epimerase/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Recombinant Proteins); EC 5.1.3.- (Carbohydrate Epimerases); EC 5.1.3.2 (UDPglucose 4-Epimerase)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170504
[Lr] Data última revisão:
170504
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170414
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0175193


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[PMID]:28351515
[Au] Autor:Bork K; Weidemann W; Berneck B; Kuchta M; Bennmann D; Thate A; Huber O; Gnanapragassam VS; Horstkorte R
[Ad] Endereço:Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Hollystraße 1, D-06114 Halle (Saale), Germany.
[Ti] Título:The expression of sialyltransferases is regulated by the bioavailability and biosynthesis of sialic acids.
[So] Source:Gene Expr Patterns;23-24:52-58, 2017 Jan.
[Is] ISSN:1872-7298
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Glycosylation is the most frequent and important post-translational modification of proteins. It occurs on specific consensus sequences but the final structure of a particular glycan is not coded on the DNA, rather it depends on the expression of the required enzymes and the availability of substrates (activated monosaccharides). Sialic acid (Sia) is the terminal monosaccharide of most glycoproteins or glycolipids (= glycoconjugates) and involved in a variety of function on molecular (e.g. determination of protein stability and half-life) and cellular level (e.g. influenza infection). Sia are synthesized in the cytosol from UDP-GlcNAc by the Roseman-Warren pathway. The key enzyme of this pathway is the UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE). Sia are transferred on glycoconjugates by a family of Golgi-located enzymes, so called sialyltransferases (ST). There are 20 (human) ST known, which all transfer CMP-activated Sia to specific acceptor-sites on glycoconjugates. The regulation of the expression of ST is still not understood. Using a GNE-deficient embryonic stem cell line, which cannot synthesize Sia endogenously and by supplementation of soluble Sia precursors, we present data that the cellular availability of Sia strongly regulates the expression of ST on the level of transcription. In summary, we suggest that the concentration of the donor substrate of sialyltransferases, which can be regarded as a sensor for the environmental conditions of a cell, regulates not only total sialylation, but also the quality of sialylation. This allows a cell to response to altered environmental conditions.
[Mh] Termos MeSH primário: Regulação Enzimológica da Expressão Gênica
Ácido N-Acetilneuramínico/biossíntese
Sialiltransferases/genética
[Mh] Termos MeSH secundário: Animais
Carboidratos Epimerases/genética
Carboidratos Epimerases/metabolismo
Células-Tronco Embrionárias/enzimologia
Células-Tronco Embrionárias/metabolismo
Camundongos
Processamento de Proteína Pós-Traducional
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.4.99.- (Sialyltransferases); EC 5.1.3.- (Carbohydrate Epimerases); EC 5.1.3.14 (UDP acetylglucosamine-2-epimerase); GZP2782OP0 (N-Acetylneuraminic Acid)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170420
[Lr] Data última revisão:
170420
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170330
[St] Status:MEDLINE



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