Base de dados : MEDLINE
Pesquisa : D08.811.913.400.450.560 [Categoria DeCS]
Referências encontradas : 975 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 98 ir para página                         

  1 / 975 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29309433
[Au] Autor:Kobayashi M; Jitoku D; Iwayama Y; Yamamoto N; Toyota T; Suzuki K; Kikuchi M; Hashimoto T; Kanahara N; Kurumaji A; Yoshikawa T; Nishikawa T
[Ad] Endereço:Department of Psychiatry and Behavioral Sciences, Graduate School of Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
[Ti] Título:Association studies of WD repeat domain 3 and chitobiosyldiphosphodolichol beta-mannosyltransferase genes with schizophrenia in a Japanese population.
[So] Source:PLoS One;13(1):e0190991, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Schizophrenia and schizophrenia-like symptoms induced by the dopamine agonists and N-methyl-D aspartate type glutamate receptor antagonists occur only after the adolescent period. Similarly, animal models of schizophrenia by these drugs are also induced after the critical period around postnatal week three. Based upon the development-dependent onsets of these psychotomimetic effects, by using a DNA microarray technique, we identified the WD repeat domain 3 (WDR3) and chitobiosyldiphosphodolichol beta-mannosyltransferase (ALG1) genes as novel candidates for schizophrenia-related molecules, whose mRNAs were up-regulated in the adult (postnatal week seven), but not in the infant (postnatal week one) rats by an indirect dopamine agonist, and phencyclidine, an antagonist of the NMDA receptor. WDR3 and other related proteins are the nuclear proteins presumably involved in various cellular activities, such as cell cycle progression, signal transduction, apoptosis, and gene regulation. ALG1 is presumed to be involved in the regulation of the protein N-glycosylation. To further elucidate the molecular pathophysiology of schizophrenia, we have evaluated the genetic association of WDR3 and ALG1 in schizophrenia. We examined 21 single nucleotide polymorphisms [SNPs; W1 (rs1812607)-W16 (rs6656360), A1 (rs8053916)-A10 (rs9673733)] from these genes using the Japanese case-control sample (1,808 schizophrenics and 2,170 matched controls). No significant genetic associations of these SNPs were identified. However, we detected a significant association of W4 (rs319471) in the female schizophrenics (allelic P = 0.003, genotypic P = 0.008). Based on a haplotype analysis, the observed haplotypes consisting of W4 (rs319471)-W5 (rs379058) also displayed a significant association in the female schizophrenics (P = 0.016). Even after correction for multiple testing, these associations remained significant. Our findings suggest that the WDR3 gene may likely be a sensitive factor in female patients with schizophrenia, and that modification of the WDR3 signaling pathway warrants further investigation as to the pathophysiology of schizophrenia.
[Mh] Termos MeSH primário: Manosiltransferases/genética
Proteínas Nucleares/genética
[Mh] Termos MeSH secundário: Adulto
Estudos de Casos e Controles
Epistasia Genética
Feminino
Seres Humanos
Japão
Masculino
Meia-Idade
Análise de Sequência com Séries de Oligonucleotídeos
Polimorfismo de Nucleotídeo Único
Esquizofrenia/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Nuclear Proteins); 0 (WDR3 protein, human); EC 2.4.1.- (Mannosyltransferases); EC 2.4.1.142 (chitobiosyldiphosphodolichol beta-mannosyltransferase)
[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:180109
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190991


  2 / 975 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28742265
[Au] Autor:Alsubhi S; Alhashem A; Faqeih E; Alfadhel M; Alfaifi A; Altuwaijri W; Alsahli S; Aldhalaan H; Alkuraya FS; Hundallah K; Mahmoud A; Alasmari A; Mutairi FA; Abduraouf H; AlRasheed L; Alshahwan S; Tabarki B
[Ad] Endereço:Division of Pediatric Neurology, Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
[Ti] Título:Congenital disorders of glycosylation: The Saudi experience.
[So] Source:Am J Med Genet A;173(10):2614-2621, 2017 Oct.
[Is] ISSN:1552-4833
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We retrospectively reviewed Saudi patients who had a congenital disorder of glycosylation (CDG). Twenty-seven Saudi patients (14 males, 13 females) from 13 unrelated families were identified. Based on molecular studies, the 27 CDG patients were classified into different subtypes: ALG9-CDG (8 patients, 29.5%), ALG3-CDG (7 patients, 26%), COG6-CDG (7 patients, 26%), MGAT2-CDG (3 patients, 11%), SLC35A2-CDG (1 patient), and PMM2-CDG (1 patient). All the patients had homozygous gene mutations. The combined carrier frequency of CDG for the encountered founder mutations in the Saudi population is 11.5 per 10,000, which translates to a minimum disease burden of 14 patients per 1,000,000. Our study provides comprehensive epidemiologic information and prevalence figures for each of these CDG in a large cohort of congenital disorder of glycosylation patients.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/genética
Defeitos Congênitos da Glicosilação/genética
Mutação
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transporte Vesicular/genética
Adolescente
Criança
Pré-Escolar
Defeitos Congênitos da Glicosilação/epidemiologia
Feminino
Glicosilação
Homozigoto
Seres Humanos
Lactente
Masculino
Manosiltransferases/genética
Proteínas de Membrana/genética
Oxigenases de Função Mista/genética
Proteínas de Transporte de Monossacarídeos/genética
N-Acetilglucosaminiltransferases/genética
Fenótipo
Estudos Retrospectivos
Arábia Saudita/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Vesicular Transport); 0 (Biomarkers, Tumor); 0 (COG6 protein, human); 0 (Membrane Proteins); 0 (Monosaccharide Transport Proteins); 0 (UDP-galactose translocator); EC 1.- (Mixed Function Oxygenases); EC 1.14.17.- (4-coumaroyl-D-glucose hydroxylase); EC 2.4.1.- (ALG3 protein, human); EC 2.4.1.- (ALG9 protein, human); EC 2.4.1.- (Mannosyltransferases); EC 2.4.1.- (N-Acetylglucosaminyltransferases); EC 2.4.1.143 (alpha-1,6-mannosyl-glycoprotein beta-1,2-N-acetylglucosaminyltransferase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180207
[Lr] Data última revisão:
180207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE
[do] DOI:10.1002/ajmg.a.38358


  3 / 975 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28743912
[Au] Autor:Gandini R; Reichenbach T; Tan TC; Divne C
[Ad] Endereço:School of Biotechnology, KTH Royal Institute of Technology, S-10691, Stockholm, Sweden.
[Ti] Título:Structural basis for dolichylphosphate mannose biosynthesis.
[So] Source:Nat Commun;8(1):120, 2017 07 25.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Protein glycosylation is a critical protein modification. In biogenic membranes of eukaryotes and archaea, these reactions require activated mannose in the form of the lipid conjugate dolichylphosphate mannose (Dol-P-Man). The membrane protein dolichylphosphate mannose synthase (DPMS) catalyzes the reaction whereby mannose is transferred from GDP-mannose to the dolichol carrier Dol-P, to yield Dol-P-Man. Failure to produce or utilize Dol-P-Man compromises organism viability, and in humans, several mutations in the human dpm1 gene lead to congenital disorders of glycosylation (CDG). Here, we report three high-resolution crystal structures of archaeal DPMS from Pyrococcus furiosus, in complex with nucleotide, donor, and glycolipid product. The structures offer snapshots along the catalytic cycle, and reveal how lipid binding couples to movements of interface helices, metal binding, and acceptor loop dynamics to control critical events leading to Dol-P-Man synthesis. The structures also rationalize the loss of dolichylphosphate mannose synthase function in dpm1-associated CDG.The generation of glycolipid dolichylphosphate mannose (Dol-P-Man) is a critical step for protein glycosylation and GPI anchor synthesis. Here the authors report the structure of dolichylphosphate mannose synthase in complex with bound nucleotide and donor to provide insight into the mechanism of Dol-P-Man synthesis.
[Mh] Termos MeSH primário: Proteínas Arqueais/metabolismo
Manose/biossíntese
Manosiltransferases/metabolismo
Pyrococcus furiosus/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Proteínas Arqueais/química
Proteínas Arqueais/genética
Sítios de Ligação/genética
Biocatálise
Cristalografia por Raios X
Manose/química
Manosiltransferases/química
Manosiltransferases/genética
Modelos Moleculares
Domínios Proteicos
Pyrococcus furiosus/enzimologia
Pyrococcus furiosus/genética
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Homologia de Sequência de Aminoácidos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Archaeal Proteins); 0 (Recombinant Proteins); EC 2.4.1.- (Mannosyltransferases); EC 2.4.1.109 (protein O-mannosyltransferase); PHA4727WTP (Mannose)
[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:170727
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-00187-2


  4 / 975 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28855252
[Au] Autor:Rahlwes KC; Ha SA; Motooka D; Mayfield JA; Baumoel LR; Strickland JN; Torres-Ocampo AP; Nakamura S; Morita YS
[Ad] Endereço:From the Department of Microbiology, University of Massachusetts, Amherst, MA 01003.
[Ti] Título:The cell envelope-associated phospholipid-binding protein LmeA is required for mannan polymerization in mycobacteria.
[So] Source:J Biol Chem;292(42):17407-17417, 2017 Oct 20.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The integrity of the distinguishing, multilaminate cell envelope surrounding mycobacteria is critical to their survival and pathogenesis. The prevalence of phosphatidylinositol mannosides in the cell envelope suggests an important role in the mycobacterial life cycle. Indeed, deletion of the gene (Δ ) encoding the first committed step in phosphatidylinositol hexamannoside biosynthesis in results in the formation of smaller colonies than wild-type colonies on Middlebrook 7H10 agar. To further investigate potential contributors to cell-envelope mannan biosynthesis while taking advantage of this colony morphology defect, we isolated spontaneous suppressor mutants of Δ that reverted to wild-type colony size. Of 22 suppressor mutants, 6 accumulated significantly shorter lipomannan or lipoarabinomannan. Genome sequencing of these mutants revealed mutations in genes involved in the lipomannan/lipoarabinomannan biosynthesis, such as those encoding the arabinosyltransferase EmbC and the mannosyltransferase MptA. Furthermore, we identified three mutants carrying a mutation in a previously uncharacterized gene, _ , that we designated Complementation of these suppressor mutants with restored the original Δ phenotypes and deletion of in wild-type resulted in smaller lipomannan, as observed in the suppressor mutants. LmeA carries a predicted N-terminal signal peptide, and density gradient fractionation and detergent extractability experiments indicated that LmeA localizes to the cell envelope. Using a lipid ELISA, we found that LmeA binds to plasma membrane phospholipids, such as phosphatidylethanolamine and phosphatidylinositol. LmeA is widespread throughout the Corynebacteriales; therefore, we concluded that LmeA is an evolutionarily conserved cell-envelope protein critical for controlling the mannan chain length of lipomannan/lipoarabinomannan.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Membrana Celular/metabolismo
Mananas/biossíntese
Manosiltransferases/metabolismo
Mycobacterium smegmatis/metabolismo
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
Membrana Celular/genética
Lipopolissacarídeos/biossíntese
Lipopolissacarídeos/genética
Mananas/genética
Manosiltransferases/genética
Mycobacterium smegmatis/genética
Fosfolipídeos/genética
Fosfolipídeos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Lipopolysaccharides); 0 (Mannans); 0 (Phospholipids); 0 (lipoarabinomannan); 0 (lipomannan); EC 2.4.1.- (Mannosyltransferases)
[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:170901
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.804377


  5 / 975 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28687598
[Au] Autor:Sheikh MO; Wells L
[Ad] Endereço:From the Complex Carbohydrate Research Center and.
[Ti] Título:Whoa man! Unexpected protein -mannosylation pathways in mammals.
[So] Source:J Biol Chem;292(27):11599-11600, 2017 Jul 07.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The recent expansion of well-characterized -mannosylated mammalian proteins beyond the archetypical example of α-dystroglycan has inspired new interest in the possibility of additional functional roles of this modification. In an effort to explore those roles, a new study now serendipitously uncovers the existence of an alternative pathway to the well-described POMT (protein -mannosyltransferase) family of -mannosyltransferases.
[Mh] Termos MeSH primário: Distroglicanas/metabolismo
Manosiltransferases/metabolismo
[Mh] Termos MeSH secundário: Animais
Distroglicanas/genética
Glicosilação
Seres Humanos
Manosiltransferases/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
146888-27-9 (Dystroglycans); EC 2.4.1.- (Mannosyltransferases); EC 2.4.1.109 (protein O-mannosyltransferase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170709
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.H117.794487


  6 / 975 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28512129
[Au] Autor:Larsen ISB; Narimatsu Y; Joshi HJ; Yang Z; Harrison OJ; Brasch J; Shapiro L; Honig B; Vakhrushev SY; Clausen H; Halim A
[Ad] Endereço:From the Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark, and.
[Ti] Título:Mammalian -mannosylation of cadherins and plexins is independent of protein -mannosyltransferases 1 and 2.
[So] Source:J Biol Chem;292(27):11586-11598, 2017 Jul 07.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Protein mannosylation is found in yeast and metazoans, and a family of conserved orthologous protein mannosyltransferases is believed to initiate this important post-translational modification. We recently discovered that the cadherin superfamily carries linked mannose ( -Man) glycans at highly conserved residues in specific extracellular cadherin domains, and it was suggested that the function of E-cadherin was dependent on the Man glycans. Deficiencies in enzymes catalyzing Man biosynthesis, including the two human protein mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix. To explore the functions of Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating Man glycosylation and the major enzyme elongating Man glycans, the protein mannose ß-1,2- -acetylglucosaminyltransferase, POMGnT1. Surprisingly, mannosylation of cadherins and protocadherins does not require POMT1 and/or POMT2 in contrast to α-dystroglycan, and moreover, the Man glycans on cadherins are not elongated. Thus, the classical and evolutionarily conserved POMT mannosylation pathway is essentially dedicated to α-dystroglycan and a few other proteins, whereas a novel mannosylation process in mammalian cells is predicted to serve the large cadherin superfamily and other proteins.
[Mh] Termos MeSH primário: Caderinas/metabolismo
Moléculas de Adesão Celular/metabolismo
Distroglicanas/metabolismo
Manosiltransferases/metabolismo
Proteínas do Tecido Nervoso/metabolismo
[Mh] Termos MeSH secundário: Animais
Células CHO
Caderinas/genética
Moléculas de Adesão Celular/genética
Cricetinae
Cricetulus
Glicosilação
Células HEK293
Seres Humanos
Manosiltransferases/genética
Proteínas do Tecido Nervoso/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cadherins); 0 (Cell Adhesion Molecules); 0 (DAG1 protein, human); 0 (Nerve Tissue Proteins); 0 (plexin); 146888-27-9 (Dystroglycans); EC 2.4.1.- (Mannosyltransferases); EC 2.4.1.109 (protein O-mannosyltransferase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170824
[Lr] Data última revisão:
170824
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170518
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.794487


  7 / 975 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28182637
[Au] Autor:Liang WC; Tian X; Yuo CY; Chen WZ; Kan TM; Su YN; Nishino I; Wong LC; Jong YJ
[Ad] Endereço:Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
[Ti] Título:Comprehensive target capture/next-generation sequencing as a second-tier diagnostic approach for congenital muscular dystrophy in Taiwan.
[So] Source:PLoS One;12(2):e0170517, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Congenital muscular dystrophy (CMD) is a heterogeneous disease entity. The detailed clinical manifestation and causative gene for each subgroup of CMD are quite variable. This study aims to analyze the phenotypes and genotypes of Taiwanese patients with CMD as the epidemiology of CMD varies among populations and has been scantly described in Asia. METHODS: A total of 48 patients suspected to have CMD were screened and categorized by histochemistry and immunohistochemistry studies. Different genetic analyses, including next-generation sequencing (NGS), were selected, based on the clinical and pathological findings. RESULTS: We identified 17 patients with sarcolemma-specific collagen VI deficiency (SSCD), 6 patients with merosin deficiency, two with reduced alpha-dystroglycan staining, and two with striking lymphocyte infiltration in addition to dystrophic change on muscle pathology. Fourteen in 15 patients with SSCD, were shown to have COL6A1, COL6A2 or COL6A3 mutations by NGS analysis; all showed marked distal hyperlaxity and normal intelligence but the overall severity was less than in previously reported patients from other populations. All six patients with merosin deficiency had mutations in LAMA2. They showed relatively uniform phenotype that were compatible with previous studies, except for higher proportion of mental retardation with epilepsy. With reduced alpha-dystroglycan staining, one patient was found to carry mutations in POMT1 while another patient carried mutations in TRAPPC11. LMNA mutations were found in the two patients with inflammatory change on muscle pathology. They were clinically characterized by neck flexion limitation and early joint contracture, but no cardiac problem had developed yet. CONCLUSION: Muscle pathology remains helpful in guiding further molecular analyses by direct sequencing of certain genes or by target capture/NGS as a second-tier diagnostic tool, and is crucial for establishing the genotype-phenotype correlation. We also determined the frequencies of the different types of CMD in our cohort which is important for the development of a specific care system for each disease.
[Mh] Termos MeSH primário: Genótipo
Sequenciamento de Nucleotídeos em Larga Escala
Distrofias Musculares
[Mh] Termos MeSH secundário: Adolescente
Adulto
Antígenos de Neoplasias/genética
Antígenos de Neoplasias/metabolismo
Grupo com Ancestrais do Continente Asiático
Criança
Colágeno Tipo VI/genética
Colágeno Tipo VI/metabolismo
Feminino
Seres Humanos
Imuno-Histoquímica
Lactente
Lamina Tipo A/genética
Lamina Tipo A/metabolismo
Laminina/genética
Laminina/metabolismo
Masculino
Manosiltransferases/genética
Manosiltransferases/metabolismo
Distrofias Musculares/diagnóstico
Distrofias Musculares/genética
Distrofias Musculares/metabolismo
Estudos Retrospectivos
Taiwan
Proteínas de Transporte Vesicular/genética
Proteínas de Transporte Vesicular/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Neoplasm); 0 (Collagen Type VI); 0 (LMNA protein, human); 0 (Lamin Type A); 0 (Laminin); 0 (TRAPPC1 protein, human); 0 (Vesicular Transport Proteins); 0 (laminin alpha 2); EC 2.4.1.- (Mannosyltransferases); EC 2.4.1.109 (protein O-mannosyltransferase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170827
[Lr] Data última revisão:
170827
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170210
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0170517


  8 / 975 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28101612
[Au] Autor:Kim YH; Kang JY; Gil JY; Kim SY; Shin KK; Kang HA; Kim JY; Kwon O; Oh DB
[Ad] Endereço:Synthetic Biology and Bioengineering Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, South Korea.
[Ti] Título:Abolishment of N-glycan mannosylphosphorylation in glyco-engineered Saccharomyces cerevisiae by double disruption of MNN4 and MNN14 genes.
[So] Source:Appl Microbiol Biotechnol;101(7):2979-2989, 2017 Apr.
[Is] ISSN:1432-0614
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Mannosylphosphorylated glycans are found only in fungi, including yeast, and the elimination of mannosylphosphates from glycans is a prerequisite for yeast glyco-engineering to produce human-compatible glycoproteins. In Saccharomyces cerevisiae, MNN4 and MNN6 genes are known to play roles in mannosylphosphorylation, but disruption of these genes does not completely remove the mannosylphosphates in N-glycans. This study was performed to find unknown key gene(s) involved in N-glycan mannosylphosphorylation in S. cerevisiae. For this purpose, each of one MNN4 and five MNN6 homologous genes were deleted from the och1Δmnn1Δmnn4Δmnn6Δ strain, which lacks yeast-specific hyper-mannosylation and the immunogenic α(1,3)-mannose structure. N-glycan profile analysis of cell wall mannoproteins and a secretory recombinant protein produced in mutants showed that the MNN14 gene, an MNN4 paralog with unknown function, is essential for N-glycan mannosylphosphorylation. Double disruption of MNN4 and MNN14 genes was enough to eliminate N-glycan mannosylphosphorylation. Our results suggest that the S. cerevisiae och1Δmnn1Δmnn4Δmnn14Δ strain, in which all yeast-specific N-glycan structures including mannosylphosphorylation are abolished, may have promise as a useful platform for glyco-engineering to produce therapeutic glycoproteins with human-compatible N-glycans.
[Mh] Termos MeSH primário: Manose/metabolismo
Proteínas de Membrana/genética
Engenharia Metabólica
Polissacarídeos/metabolismo
Proteínas de Saccharomyces cerevisiae/genética
Saccharomyces cerevisiae/genética
[Mh] Termos MeSH secundário: Parede Celular/metabolismo
Seres Humanos
Manose/química
Manose/genética
Manosefosfatos/metabolismo
Manosiltransferases/deficiência
Manosiltransferases/genética
Manosiltransferases/metabolismo
Glicoproteínas de Membrana/genética
Proteínas de Membrana/metabolismo
Fosforilação
Proteínas Recombinantes
Saccharomyces cerevisiae/metabolismo
Proteínas de Saccharomyces cerevisiae/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MNN4 protein, S cerevisiae); 0 (Mannosephosphates); 0 (Membrane Glycoproteins); 0 (Membrane Proteins); 0 (Polysaccharides); 0 (Recombinant Proteins); 0 (Saccharomyces cerevisiae Proteins); EC 2.4.1.- (MNN6 protein, S cerevisiae); EC 2.4.1.- (Mannosyltransferases); PHA4727WTP (Mannose)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170405
[Lr] Data última revisão:
170405
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170120
[St] Status:MEDLINE
[do] DOI:10.1007/s00253-017-8101-3


  9 / 975 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27722917
[Au] Autor:He Z; Luo L; Keyhani NO; Yu X; Ying S; Zhang Y
[Ad] Endereço:College of Plant Protection, Biotechnology Research Center, Southwest University, Chongqing, 400715, People's Republic of China.
[Ti] Título:The C-terminal MIR-containing region in the Pmt1 O-mannosyltransferase restrains sporulation and is dispensable for virulence in Beauveria bassiana.
[So] Source:Appl Microbiol Biotechnol;101(3):1143-1161, 2017 Feb.
[Is] ISSN:1432-0614
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Protein O-mannosyltransferases (Pmts) belong to a highly conserved protein family responsible for the initiation of O-glycosylation of many proteins. Pmts contain one dolichyl-phosphate-mannose-protein mannosyltransferases (PMT) domain and three MIR motifs (mannosyltransferase, inositol triphosphate, and ryanodine receptor) that are essential for activity in yeast. We report that in the insect fungal pathogen, Beauveria bassiana, deletion of the C-terminal Pmt1 MIR-containing region (Pmt1∆ ) does not alter O-mannosyltransferase activity, but does increase total cell wall protein O-mannosylation levels and results in phenotypic changes in fungal development and cell wall stability. B. bassiana mutants harboring the Pmt1 ∆ mutation displayed a significant increase in conidiation with up-regulation of conidiation-associated genes and an increase in biomass accumulation as compared to the wild-type parent. However, decreased vegetative growth and blastospore production was noted, and Pmt1 ∆ mutants were altered in cell wall composition and cell surface features. Insect bioassays revealed little effect on virulence for the Pmt1 ∆ strain via cuticle infection or intrahemocoel injection assays, although differences in hyphal body differentiation in the host hemolymph and up-regulation of virulence-associated genes were noted. These data suggest novel roles for Pmt1 in negatively regulating conidiation and demonstrate that the C-terminal Pmt1 MIR-containing region is dispensable for enzymatic activity and organismal virulence.
[Mh] Termos MeSH primário: Beauveria/genética
Beauveria/fisiologia
Manosiltransferases/química
Manosiltransferases/metabolismo
[Mh] Termos MeSH secundário: Animais
Beauveria/patogenicidade
Bioensaio
Biomassa
Parede Celular/fisiologia
Insetos/microbiologia
Manosiltransferases/genética
Mutação
Deleção de Sequência
Esporos Fúngicos/genética
Esporos Fúngicos/crescimento & desenvolvimento
Regulação para Cima
Virulência
Fatores de Virulência/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Virulence Factors); EC 2.4.1.- (Mannosyltransferases); EC 2.4.1.109 (protein O-mannosyltransferase)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161011
[St] Status:MEDLINE
[do] DOI:10.1007/s00253-016-7894-9


  10 / 975 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27670784
[Au] Autor:Li ST; Wang N; Xu S; Yin J; Nakanishi H; Dean N; Gao XD
[Ad] Endereço:Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China. Electronic address: lishe520@126.com.
[Ti] Título:Quantitative study of yeast Alg1 beta-1, 4 mannosyltransferase activity, a key enzyme involved in protein N-glycosylation.
[So] Source:Biochim Biophys Acta;1861(1 Pt A):2934-2941, 2017 01.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Asparagine (N)-linked glycosylation begins with a stepwise synthesis of the dolichol-linked oligosaccharide (DLO) precursor, Glc3Man9GlcNAc2-PP-Dol, which is catalyzed by a series of endoplasmic reticulum membrane-associated glycosyltransferases. Yeast ALG1 (asparagine-linked glycosylation 1) encodes a ß-1, 4 mannosyltransferase that adds the first mannose onto GlcNAc2-PP-Dol to produce a core trisaccharide Man1GlcNAc2-PP-Dol. ALG1 is essential for yeast viability, and in humans mutations in the ALG1 cause congenital disorders of glycosylation known as ALG1-CDG. Alg1 is difficult to purify because of its low expression level and as a consequence, has not been well studied biochemically. Here we report a new method to purify recombinant Alg1 in high yield, and a mass spectral approach for accurately measuring its ß-1, 4 mannosyltransferase activity. METHODS: N-terminally truncated yeast His-tagged Alg1 protein was expressed in Escherichia coli and purified by HisTrap HP affinity chromatography. In combination with LC-MS technology, we established a novel assay to accurately measure Alg1 enzyme activity. In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the ß-1, 4 mannosyl transfer reaction. RESULTS: Using purified Alg1, its biochemical characteristics were investigated, including the apparent K and V values for acceptor, optimal conditions of activity, and the specificity of its nucleotide sugar donor. Furthermore, the effect of ALG1-CDG mutations on enzyme activity was also measured. GENERAL SIGNIFICANCE: This work provides an efficient method for production of Alg1 and a new MS-based quantitative assay of its activity.
[Mh] Termos MeSH primário: Manosiltransferases/metabolismo
Saccharomyces cerevisiae/enzimologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Western Blotting
Cromatografia Líquida
Dissacarídeos/química
Dissacarídeos/metabolismo
Eletroforese em Gel de Poliacrilamida
Glicosilação
Manosiltransferases/química
Espectrometria de Massas
Proteínas Mutantes/química
Proteínas Mutantes/isolamento & purificação
Proteínas Mutantes/metabolismo
Proteínas Recombinantes/biossíntese
Proteínas Recombinantes/isolamento & purificação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Disaccharides); 0 (Mutant Proteins); 0 (Recombinant Proteins); 0 (phytanylpyrophosphoryl-N,N'-diacetylchitobioside); EC 2.4.1.- (Mannosyltransferases); EC 2.4.1.142 (chitobiosyldiphosphodolichol beta-mannosyltransferase)
[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:161106
[St] Status:MEDLINE



página 1 de 98 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde