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Xylosyltransferase 2

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https://www.readbyqxmd.com/read/28952517/engineering-of-cho-cells-for-the-production-of-recombinant-glycoprotein-vaccines-with-xylosylated-n-glycans
#1
Grit Sandig, Hans Henning von Horsten, Lars Radke, Véronique Blanchard, Marcus Frohme, Christoph Giese, Volker Sandig, Stephan Hinderlich
Xylose is a general component of O-glycans in mammals. Core-xylosylation of N-glycans is only found in plants and helminth. Consequently, xylosylated N-glycans cause immunological response in humans. We have used the F-protein of the human respiratory syncytial virus (RSV), one of the main causes of respiratory tract infection in infants and elderly, as a model protein for vaccination. The RSV-F protein was expressed in CHO-DG44 cells, which were further modified by co-expression of β1,2-xylosyltransferase from Nicotiana tabacum...
April 28, 2017: Bioengineering
https://www.readbyqxmd.com/read/28396675/inactivation-of-the-%C3%AE-1-2-xylosyltransferase-and-the-%C3%AE-1-3-fucosyltransferase-genes-in-nicotiana-tabacum-by-2-cells-by-a-multiplex-crispr-cas9-strategy-results-in-glycoproteins-without-plant-specific-glycans
#2
Sébastien Mercx, Nicolas Smargiasso, François Chaumont, Edwin De Pauw, Marc Boutry, Catherine Navarre
Plants or plant cells can be used to produce pharmacological glycoproteins such as antibodies or vaccines. However these proteins carry N-glycans with plant-typical residues [β(1,2)-xylose and core α(1,3)-fucose], which can greatly impact the immunogenicity, allergenicity, or activity of the protein. Two enzymes are responsible for the addition of plant-specific glycans: β(1,2)-xylosyltransferase (XylT) and α(1,3)-fucosyltransferase (FucT). Our aim consisted of knocking-out two XylT genes and four FucT genes (12 alleles altogether) in Nicotiana tabacum BY-2 suspension cells using CRISPR/Cas9...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28371609/trastuzumab-and-pertuzumab-plant-biosimilars-modification-of-asn297-linked-glycan-of-the-mabs-produced-in-a-plant-with-fucosyltransferase-and-xylosyltransferase-gene-knockouts
#3
T V Komarova, E V Sheshukova, E N Kosobokova, M V Serebryakova, V S Kosorukov, V N Tashlitsky, Y L Dorokhov
Plant biosimilars of anticancer therapeutic antibodies are of interest not only because of the prospects of their practical use, but also as an instrument and object for study of plant protein glycosylation. In this work, we first designed a pertuzumab plant biosimilar (PPB) and investigated the composition of its Asn297-linked glycan in comparison with trastuzumab plant biosimilar (TPB). Both biosimilars were produced in wild-type (WT) Nicotiana benthamiana plant (PPB-WT and TPB-WT) and transgenic ΔXTFT N...
April 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27930836/hepatitis-c-virus-infection-propagates-through-interactions-between-syndecan-1-and-cd81-and-impacts-the-hepatocyte-glycocalyx
#4
Boyan Grigorov, Emma Reungoat, Alice Gentil Dit Maurin, Mihayl Varbanov, Julie Blaising, Maud Michelet, Rachel Manuel, Romain Parent, Birke Bartosch, Fabien Zoulim, Florence Ruggiero, Eve-Isabelle Pécheur
The hepatitis C virus (HCV) infects hepatocytes after binding to heparan sulfate proteoglycans, in particular Syndecan-1, followed by recognition of the tetraspanin CD81 and other receptors. Heparan sulfate proteoglycans are found in a specific microenvironment coating the hepatocyte surface called the glycocalyx and are receptors for extracellular matrix proteins, cytokines, growth factors, lipoproteins, and infectious agents. We investigated the mutual influence of HCV infection on the glycocalyx and revealed new links between Syndecan-1 and CD81...
May 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/27881841/novel-and-recurrent-xylt1-mutations-in-two-turkish-families-with-desbuquois-dysplasia-type-2
#5
Long Guo, Nursel H Elcioglu, Aritoshi Iida, Yasemin K Demirkol, Seda Aras, Naomichi Matsumoto, Gen Nishimura, Noriko Miyake, Shiro Ikegawa
Desbuquois dysplasia (DBQD) is an autosomal recessive skeletal disorder characterized by growth retardation, joint laxity, short extremities, and progressive scoliosis. DBQD is classified into two types based on the presence (DBQD1) or absence (DBQD2) of characteristic hand abnormalities. CANT1 mutations have been reported in both DBQD1 and DBQD2. Recently, mutations in the gene encoding xylosyltransferase 1 (XYLT1) were identified in several families with DBQD2. In this study, we performed whole-exome sequencing in two Turkish families with DBQD2...
March 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/27616058/discovery-of-novel-xylosides-in-co-culture-of-basidiomycetes-trametes-versicolor-and-ganoderma-applanatum-by-integrated-metabolomics-and-bioinformatics
#6
Lu Yao, Li-Ping Zhu, Xiao-Yan Xu, Ling-Ling Tan, Martin Sadilek, Huan Fan, Bo Hu, Xiao-Ting Shen, Jie Yang, Bin Qiao, Song Yang
Transcriptomic analysis of cultured fungi suggests that many genes for secondary metabolite synthesis are presumably silent under standard laboratory condition. In order to investigate the expression of silent genes in symbiotic systems, 136 fungi-fungi symbiotic systems were built up by co-culturing seventeen basidiomycetes, among which the co-culture of Trametes versicolor and Ganoderma applanatum demonstrated the strongest coloration of confrontation zones. Metabolomics study of this co-culture discovered that sixty-two features were either newly synthesized or highly produced in the co-culture compared with individual cultures...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27193738/truncations-of-xyloglucan-xylosyltransferase-2-provide-insights-into-the-roles-of-the-n-and-c-terminus
#7
Alan T Culbertson, Adrienne L Smith, Matthew D Cook, Olga A Zabotina
Xyloglucan is the most abundant hemicellulose in the primary cell wall of dicotyledonous plants. In Arabidopsis, three xyloglucan xylosyltransferases, XXT1, XXT2, and XXT5, participate in xylosylation of the xyloglucan backbone. Despite the importance of these enzymes, there is a lack of information on their structure and the critical residues required for substrate binding and transferase activity. In this study, the roles of different domains of XX2 in protein expression and catalytic activity were investigated by constructing a series of N- and C-terminal truncations...
August 2016: Phytochemistry
https://www.readbyqxmd.com/read/27146522/a-homology-model-of-xyloglucan-xylosyltransferase-2-reveals-critical-amino-acids-involved-in-substrate-binding
#8
Alan T Culbertson, Alesia A Tietze, Daniel Tietze, Yi-Hsiang Chou, Adrienne L Smith, Zachary T Young, Olga A Zabotina
In dicotyledonous plants, xyloglucan (XyG) is the most abundant hemicellulose of the primary cell wall. The enzymes involved in XyG biosynthesis have been identified through reverse-genetics and activity was characterized by heterologous expression. Currently, there is no information on the atomic structures or amino acids involved in activity or substrate binding of any of the Golgi-localized XyG biosynthetic enzymes. A homology model of the xyloglucan xylosyltransferase 2 (XXT2) catalytic domain was built on the basis of the crystal structure of A64Rp...
May 4, 2016: Glycobiology
https://www.readbyqxmd.com/read/27030147/exome-sequencing-reveals-two-novel-compound-heterozygous-xylt1-mutations-in-a-polish-patient-with-desbuquois-dysplasia-type-2-and-growth-hormone-deficiency
#9
Aleksander Jamsheer, Ewelina M Olech, Kazimierz Kozłowski, Marek Niedziela, Anna Sowińska-Seidler, Monika Obara-Moszyńska, Anna Latos-Bieleńska, Marek Karczewski, Tomasz Zemojtel
Desbuquois dysplasia type 2 (DBQD2) is a rare recessively inherited skeletal genetic disorder characterized by severe prenatal and postnatal growth retardation, generalized joint laxity with dislocation of large joints and facial dysmorphism. The condition was recently described to result from autosomal recessive mutations in XYLT1, encoding the enzyme xylosyltransferase-1. In this paper, we report on a Polish patient with DBQD2 who presented with severe short stature of prenatal onset, joint laxity, psychomotor retardation and multiple radiological abnormalities including short metacarpals, advanced bone age and exaggerated trochanters...
July 2016: Journal of Human Genetics
https://www.readbyqxmd.com/read/26027496/homozygosity-for-frameshift-mutations-in-xylt2-result-in-a-spondylo-ocular-syndrome-with-bone-fragility-cataracts-and-hearing-defects
#10
Craig F Munns, Somayyeh Fahiminiya, Nabin Poudel, Maria Cristina Munteanu, Jacek Majewski, David O Sillence, Jordan P Metcalf, Andrew Biggin, Francis Glorieux, François Fassier, Frank Rauch, Myron E Hinsdale
Heparan and chondroitin/dermatan sulfated proteoglycans have a wide range of roles in cellular and tissue homeostasis including growth factor function, morphogen gradient formation, and co-receptor activity. Proteoglycan assembly initiates with a xylose monosaccharide covalently attached by either xylosyltransferase I or II. Three individuals from two families were found that exhibited similar phenotypes. The index case subjects were two brothers, individuals 1 and 2, who presented with osteoporosis, cataracts, sensorineural hearing loss, and mild learning defects...
June 4, 2015: American Journal of Human Genetics
https://www.readbyqxmd.com/read/26025522/the-rice-rcn11-gene-encodes-%C3%AE-1-2-xylosyltransferase-and-is-required-for-plant-responses-to-abiotic-stresses-and-phytohormones
#11
Sho Takano, Shuichi Matsuda, Atsushi Funabiki, Jun-ichi Furukawa, Takaki Yamauchi, Yoshihiko Tokuji, Mikio Nakazono, Yasuro Shinohara, Itsuro Takamure, Kiyoaki Kato
Seed germination rates and plant development and growth under abiotic stress are important aspects of crop productivity. Here, our characterization of the rice (Oryza sativa L.) mutant reduced culm number11 (rcn11) showed that RCN11 controls growth of plants exposed to abnormal temperature, salinity and drought conditions. RCN11 also mediates root aerenchyma formation under oxygen-deficient conditions and ABA sensitivity during seed germination. Molecular studies showed that the rcn11 mutation resulted from a 966-bp deletion that caused loss of function of β1,2-xylosyltransferase (OsXylT)...
July 2015: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/26011187/multiplexed-targeted-gene-editing-in-nicotiana-benthamiana-for-glyco-engineering-and-monoclonal-antibody-production
#12
Jin Li, Thomas J Stoddard, Zachary L Demorest, Pierre-Olivier Lavoie, Song Luo, Benjamin M Clasen, Frederic Cedrone, Erin E Ray, Andrew P Coffman, Aurelie Daulhac, Ann Yabandith, Adam J Retterath, Luc Mathis, Daniel F Voytas, Marc-André D'Aoust, Feng Zhang
Biopharmaceutical glycoproteins produced in plants carry N-glycans with plant-specific residues core α(1,3)-fucose and β(1,2)-xylose, which can significantly impact the activity, stability and immunogenicity of biopharmaceuticals. In this study, we have employed sequence-specific transcription activator-like effector nucleases (TALENs) to knock out two α(1,3)-fucosyltransferase (FucT) and the two β(1,2)-xylosyltransferase (XylT) genes within Nicotiana benthamiana to generate plants with improved capacity to produce glycoproteins devoid of plant-specific residues...
February 2016: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/25936869/uv-irradiation-induced-production-of-monoglycosylated-biglycan-through-downregulation-of-xylosyltransferase-1-in-cultured-human-dermal-fibroblasts
#13
Cheng Long Jin, Jang-Hee Oh, Mira Han, Min Kyeong Shin, Cheng Yao, Chi-Hyun Park, Zhe Hu Jin, Jin Ho Chung
BACKGROUND: Biglycan (BGN) is a proteoglycan composed of a 42-kDa core protein and two glycosaminoglycan (GAG) chains, and known to be involved in structural, space-filling functions and many physiological regulations in the skin. OBJECTIVE: To investigate ultraviolet (UV) irradiation-induced changes of BGN protein and its GAG chain synthesis in cultured human dermal fibroblasts. METHODS: UV irradiation-induced or xylosyltransferase (XYLT) 1 siRNA-mediated smaller-sized protein bands detected by Western blot using BGN antibodies were identified as monoglycosylated forms of BGN, using BGN siRNA-mediated knockdown and chondroitinase ABC (ChABC)...
July 2015: Journal of Dermatological Science
https://www.readbyqxmd.com/read/25748573/xylosyltransferase-ii-is-the-predominant-isoenzyme-which-is-responsible-for-the-steady-state-level-of-xylosyltransferase-activity-in-human-serum
#14
Joachim Kuhn, Christian Götting, Brendan J Beahm, Carolyn R Bertozzi, Isabel Faust, Patricia Kuzaj, Cornelius Knabbe, Doris Hendig
In mammals, two active xylosyltransferase isoenzymes (EC 2.4.2.16) exist. Both xylosyltransferases I and II (XT-I and XT-II) catalyze the transfer of xylose from UDP-xylose to select serine residues in the proteoglycan core protein. Altered XT activity in human serum was found to correlate directly with various diseases such as osteoarthritis, systemic sclerosis, liver fibrosis, and pseudoxanthoma elasticum. To interpret the significance of the enzyme activity alteration observed in disease states it is important to know which isoenzyme is responsible for the XT activity in serum...
April 10, 2015: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/25604050/expression-of-heterologous-xyloglucan-xylosyltransferases-in-arabidopsis-to-investigate-their-role-in-determining-xyloglucan-xylosylation-substitution-patterns
#15
Nasim Mansoori, Alex Schultink, Julia Schubert, Markus Pauly
Putative XyG xylosyltransferases from Tropaeolum majus (nasturtium) and Solanum lycopersicum (tomato) homologous to characterized Arabidopsis genes were identified and shown to functionally complement Arabidopsis mutants lacking xyloglucan demonstrating they represent xyloglucan xylosyltransferases. Xyloglucan is a major hemicellulose in the plant cell wall and is important for the structural organization of the wall. The fine structure of xyloglucan can vary dependent on plant species and tissue type. Most vascular seed-bearing plants including Arabidopsis thaliana and nasturtium (Tropaeolum majus) have a xyloglucan structure, in which three out of four backbone glucosyl-residues are substituted with xylosyl-residues...
May 2015: Planta
https://www.readbyqxmd.com/read/25392066/protein-protein-interactions-among-xyloglucan-synthesizing-enzymes-and-formation-of-golgi-localized-multiprotein-complexes
#16
Yi-Hsiang Chou, Gennady Pogorelko, Zachary T Young, Olga A Zabotina
Arabidopsis thaliana xyloglucan has an XXXG structure, with branches of xylosyl residues, β-D-galacosyl-(1,2)-α-d-xylosyl motifs and fucosylated β-D-galactosyl-(1,2)-α-D-xylosyl motifs. Most of the enzymes involved in xyloglucan biosynthesis in Arabidopsis have been identified, including the glucan synthase CSLC4 (cellulose synthase-like C4), three xylosyltransferases (XXT1, XXT2 and XXT5), two galactosyltransferases (MUR3 and XLT2) and the fucosyltransferase FUT1. The XXTs and CSLC4 form homo- and heterocomplexes and were proposed to co-localize in the same complex, but the organization of the other xyloglucan-synthesizing enzymes remains unclear...
February 2015: Plant & Cell Physiology
https://www.readbyqxmd.com/read/25098771/complex-cooperative-functions-of-heparan-sulfate-proteoglycans-shape-nervous-system-development-in-caenorhabditis-elegans
#17
Carlos A Díaz-Balzac, María I Lázaro-Peña, Eillen Tecle, Nathali Gomez, Hannes E Bülow
The development of the nervous system is a complex process requiring the integration of numerous molecular cues to form functional circuits. Many cues are regulated by heparan sulfates, a class of linear glycosaminoglycan polysaccharides. These sugars contain distinct modification patterns that regulate protein-protein interactions. Misexpressing the homolog of KAL-1/anosmin-1, a neural cell adhesion molecule mutant in Kallmann syndrome, in Caenorhabditis elegans causes a highly penetrant, heparan sulfate-dependent axonal branching phenotype in AIY interneurons...
October 2014: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/25024048/blood-cells-transcriptomics-as-source-of-potential-biomarkers-of-articular-health-improvement-effects-of-oral-intake-of-a-rooster-combs-extract-rich-in-hyaluronic-acid
#18
Juana Sánchez, M Luisa Bonet, Jaap Keijer, Evert M van Schothorst, Ingrid Mölller, Carles Chetrit, Daniel Martinez-Puig, Andreu Palou
The aim of the study was to explore peripheral blood gene expression as a source of biomarkers of joint health improvement related to glycosaminoglycan (GAG) intake in humans. Healthy individuals with joint discomfort were enrolled in a randomized, double-blind, placebo-controlled intervention study in humans. Subjects ate control yoghurt or yoghurt supplemented with a recently authorized novel food in Europe containing hyaluronic acid (65 %) from rooster comb (Mobilee™ as commercial name) for 90 days. Effects on functional quality-of-life parameters related to joint health were assessed...
September 2014: Genes & Nutrition
https://www.readbyqxmd.com/read/24834920/mutation-in-xyloglucan-6-xylosytransferase-results-in-abnormal-root-hair-development-in-oryza-sativa
#19
Chuang Wang, Shuai Li, Sophia Ng, Baocai Zhang, Yihua Zhou, James Whelan, Ping Wu, Huixia Shou
Root hairs are important for nutrient uptake, anchorage, and plant-microbe interactions. From a population of rice (Oryza sativa) mutagenized by ethyl methanesulfonate (EMS), a short root hair2 (srh2) mutant was identified. In hydroponic culture, srh2 seedlings were significantly reduced in root hair length. Bubble-like extrusions and irregular epidermal cells were observed at the tips of srh2 root hairs when grown under acidic conditions, suggesting the possible reduction of the tensile strength of the cell wall in this mutant...
August 2014: Journal of Experimental Botany
https://www.readbyqxmd.com/read/24794851/deletion-of-plant-specific-sugar-residues-in-plant-n-glycans-by-repression-of-gdp-d-mannose-4-6-dehydratase-and-%C3%AE-1-2-xylosyltransferase-genes
#20
Kouki Matsuo, Uiko Kagaya, Noriko Itchoda, Noriko Tabayashi, Takeshi Matsumura
Production of pharmaceutical glycoproteins, such as therapeutic antibodies and cytokines, in plants has many advantages in safety and reduced costs. However, plant-made glycoproteins have N-glycans with plant-specific sugar residues (core β-1,2-xylose and α-1,3-fucose) and a Lewis a (Le(a)) epitope, Galβ(1-3)[Fucα(1-4)]GlcNAc. Because it is likely that these sugar residues and glycan structures are immunogenic, many attempts have been made to delete them. Previously, we reported the simultaneous deletion of the plant-specific core α-1,3-fucose and α-1,4-fucose residues in Le(a) epitopes by repressing the GDP-D-mannose 4,6-dehydratase (GMD) gene, which is associated with GDP-L-fucose biosynthesis, in Nicotiana benthamiana plants (rGMD plants, renamed to ΔGMD plants) (Matsuo and Matsumura, Plant Biotechnol...
October 2014: Journal of Bioscience and Bioengineering
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