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Glycobiology

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https://www.readbyqxmd.com/read/29878112/addicted-to-sugar-roles-of-glycans-in-the-order-mononegavirales
#1
Victoria Ortega, Jacquelyn A Stone, Erik M Contreras, Ronald M Iorio, Hector C Aguilar
Glycosylation is a biologically important protein modification process by which a carbohydrate chain is enzymatically added to a protein at a specific amino acid residue. This process plays roles in many cellular functions, including intracellular trafficking, cell-cell signaling, protein folding, and receptor binding. While glycosylation is a common host cell process, it is utilized by many pathogens as well. Protein glycosylation is widely employed by viruses for both host invasion and evasion of host immune responses...
June 6, 2018: Glycobiology
https://www.readbyqxmd.com/read/29878110/structural-basis-of-oligosaccharide-processing-by-glycosaminoglycan-sulfotransferases
#2
Tarsis F Gesteira, Vivien J Coulson-Thomas
Heparan sulfate (HS) is a sulfated polysaccharide that plays a key role in morphogenesis, physiology and pathogenesis. The biosynthesis of HS takes place in the Golgi apparatus by a group of enzymes that polymerize, epimerize and sulfate the sugar chain. This biosynthetic process introduces varying degrees of sulfate substitution, which are tightly regulated and directly dictate binding specificity to different cytokines, morphogens and growth factors. Here we report the use of molecular dynamics simulations to investigate the dynamics of substrate recognition of two glycosaminoglycan (GAG) sulfotransferases, N-deacetylase-N-sulfotransferase and 2-O-sulfotransferase to the HS chain during the biosynthetic process...
June 6, 2018: Glycobiology
https://www.readbyqxmd.com/read/29873711/conserved-residues-arg188-and-asp302-are-critical-for-active-site-organization-and-catalysis-in-human-abo-h-blood-group-a-and-b-glycosyltransferases
#3
Susannah M L Gagnon, Max S G Legg, Robert Polakowski, James A Letts, Mattias Persson, Shuangjun Lin, Ruixiang Blake Zheng, Brian Rempel, Brock Schuman, Omid Haji-Ghassemi, Svetlana N Borisova, Monica M Palcic, Stephen V Evans
Homologous glycosyltransferases GTA and GTB perform the final step in human ABO(H) blood group A and B antigen synthesis by transferring the sugar moiety from donor UDP-GalNAc/UDP-Gal to the terminal H antigen disaccharide acceptor. Like other GT-A fold family 6 glycosyltransferases, GTA and GTB undergo major conformational changes in two mobile regions, the C-terminal tail and internal loop, to achieve the closed, catalytic state. These changes are known to establish a salt bridge network among conserved active site residues Arg188, Asp211, and Asp302, which move to accommodate a series of discrete donor conformations while promoting loop ordering and formation of the closed enzyme state...
June 5, 2018: Glycobiology
https://www.readbyqxmd.com/read/29800297/fine-tuning-the-structure-of-glycosaminoglycans-in-living-cells-using-xylosides
#4
Andrea Persson, Ulf Ellervik, Katrin Mani
Xylosides can induce the formation and secretion of xyloside-primed glycosaminoglycans when administered to living cells; however, their impact on the detailed glycosaminoglycan structure remains unknown. Here, we have systematically investigated how the xyloside concentration, and the type of xyloside, as well as the cell type, influenced the structure of xyloside-primed glycosaminoglycans in terms of the heparan sulfate and chondroitin/dermatan sulfate proportion and disaccharide composition. We found that although greatest influence was exerted by the cell type, both the xyloside concentration and type of xyloside impacted the proportion of heparan sulfate and the complexity of chondroitin/dermatan sulfate...
May 24, 2018: Glycobiology
https://www.readbyqxmd.com/read/29800278/recent-approaches-for-directly-profiling-cell-surface-sialoform
#5
Xiaoqing Zhang, Huan Nie, Joshua Whited, Dan Wang, Yu Li, Xue-Long Sun
Sialic acids (SAs) are nine-carbon monosaccharides existing at the terminal location of glycan structures on the cell surface and secreted glycoconjugates. The expression levels and linkages of SAs on cells and tissues, collectively known as sialoform, present the hallmark of the cells and tissues of different systems and conditions. Accordingly, detecting or profiling cell surface sialoforms is very critical for understanding the function of cell surface glycans and glycoconjugates and even the molecular mechanisms of their underlying biological processes...
May 24, 2018: Glycobiology
https://www.readbyqxmd.com/read/29800150/through-the-barricades-overcoming-the-barriers-to-effective-antibody-based-cancer-therapeutics
#6
Martin Dalziel, Stephen A Beers, Mark S Cragg, Max Crispin
Since the turn of the century, cancer therapy has undergone a transformation in terms of new treatment modalities and renewed optimism in achieving long-lived tumour control and even cure. This is, in large part, thanks to the widespread incorporation of monoclonal antibodies (mAbs) into standard treatment regimens. These new therapies have, across many settings, significantly contributed to improved clinical responses, patient quality of life and survival. Moreover, the flexibility of the antibody platform has led to the development of a wide range of innovative and combinatorial therapies that continue to augment the clinician's armoury...
May 24, 2018: Glycobiology
https://www.readbyqxmd.com/read/29800149/tca-cycle-powered-synthesis-of-fucosylated-oligosaccharides
#7
Ningzi Guan, Hyun-Dong Shin, Lingfeng Long, Parastoo Azadi, Rachel Chen
Microbial catalysis has recently emerged as one of the most promising approaches in oligosaccharide synthesis. However, despite significant progresses, microbial synthesis still requires much improvement in efficiency and in reduction of process complexity. Additionally, given the stunning diversity and many varied applications of glycans, broadening the range of glycans accessible via microbial synthesis is of paramount importance. Major challenges in microbial synthesis include catabolite repression and high cellular energy requirement...
May 24, 2018: Glycobiology
https://www.readbyqxmd.com/read/29796630/identification-of-serum-glycoprotein-ligands-for-the-immunomodulatory-receptor-blood-dendritic-cell-antigen-2
#8
Jong-Won Kim, James Budzak, Yu Liu, Sabine A F Jégouzo, Kurt Drickamer, Maureen E Taylor
Blood dendritic cell antigen 2 (BDCA-2) is a C-type lectin found on the surface of plasmacytoid dendritic cells. It functions as a glycan-binding receptor that down-regulates production of type I interferons and thus plays a role in oligosaccharide-mediated immunomodulation. The carbohydrate-recognition domain in BDCA-2 binds selectively to galactose-terminated bi-antennary glycans. Because the plasmacytoid dendritic cells function in a plasma environment rich in glycoproteins, experiments have been undertaken to identify endogenous ligands for BDCA-2...
May 23, 2018: Glycobiology
https://www.readbyqxmd.com/read/29796594/streptococcal-siglec-like-adhesins-recognize-different-subsets-of-human-plasma-glycoproteins-implications-for-infective-endocarditis
#9
Barbara A Bensing, Qiongyu Li, Dayoung Park, Carlito B Lebrilla, Paul M Sullam
Streptococcus gordonii and Streptococcus sanguinis are typically found among the normal oral microbiota, but can also cause infective endocarditis. These organisms express cell-surface serine-rich repeat adhesins containing "Siglec-like" binding regions (SLBRs) that mediate attachment to α2-3 linked sialic acids on human glycoproteins. Two known receptors for the Siglec-like adhesins are the salivary mucin MG2/MUC7 and platelet GPIbα, and the interaction of streptococci with these targets may contribute to oral colonization and endocarditis, respectively...
May 23, 2018: Glycobiology
https://www.readbyqxmd.com/read/29796665/a-unique-fucosylated-chondroitin-sulfate-type-ii-with-strikingly-homogeneous-and-neatly-distributed-%C3%AE-fucose-branches
#10
Paulo A G Soares, Kátia A Ribeiro, Ana P Valente, Nina V Capillé, Stephan-Nicollas M C G Oliveira, Ana M F Tovar, Mariana S Pereira, Eduardo Vilanova, Paulo A S Mourão
Fucosylated chondroitin sulfates (FCSs) and sulfated fucans (SFs) are conspicuous components of the body-wall of sea cucumbers (Holothuroidea). FCSs are composed of a central core of chondroitin sulfate decorated with branches of mono- or mono- and disaccharides of α-fucose (FCSs type I and II, respectively). FCSs type II have heterogeneous and irregularly distributed α-fucose branches; however, the novel FCS type II from Holothuria lentiginosa described herein via solution nuclear magnetic resonance has strikingly homogeneous α-fucose branches neatly distributed along its chondroitin sulfate core...
May 17, 2018: Glycobiology
https://www.readbyqxmd.com/read/29757381/the-parasitic-nematode-oesophagostomum-dentatum-synthesizes-unusual-glycosaminoglycan-like-o-glycans
#11
Jorick Vanbeselaere, Shi Yan, Anja Joachim, Katharina Paschinger, Iain B H Wilson
O-glycosylation is probably one of the most varied sets of post-translational modifications across all organisms, but amongst the most refractory to analyse. In animals, O-xylosylation of serine residues represents the first stage in the synthesis of glycosaminoglycans, whose repeat regions are generally analysed as fragments resulting from enzymatic or chemical degradation, whereas their core regions can be isolated by β-elimination or endo-β-xylosidase digestion. In the present study, we show that hydrazinolysis can be employed for release of glycosaminoglycan-type oligosaccharides from nematodes prior to fluorescent labelling with 2-aminopyridine...
May 11, 2018: Glycobiology
https://www.readbyqxmd.com/read/29757379/quiescin-sulfhydryl-oxidase-1-qsox1-glycosite-mutation-perturbs-secretion-but-not-golgi-localization
#12
Ben Horowitz, Gabriel Javitt, Tal Ilani, Yair Gat, David Morgenstern, Frederic A Bard, Deborah Fass
Quiescin sulfhydryl oxidase 1 (QSOX1) catalyzes the formation of disulfide bonds in protein substrates. Unlike other enzymes with related activities, which are commonly found in the endoplasmic reticulum, QSOX1 is localized to the Golgi apparatus or secreted. QSOX1 is upregulated in quiescent fibroblast cells and secreted into the extracellular environment, where it contributes to extracellular matrix assembly. QSOX1 is also upregulated in adenocarcinomas, though the extent to which it is secreted in this context is currently unknown...
May 11, 2018: Glycobiology
https://www.readbyqxmd.com/read/29718295/genetic-and-enzymatic-characterization-of-3-o-sulfotransferase-snps-associated-with-plasmodium-falciparum-parasitaemia
#13
Ngoc Thy Nguyen, Romain R Vivès, Magali Torres, Vincent Delauzun, Els Saesen, Véronique Roig-Zamboni, Hugues Lortat-Jacob, Pascal Rihet, Yves Bourne
The HS3ST3A1/B1 genes encode two homologous 3-O-sulfotransferases involved in the late modification step during heparan sulfate (HS) biosynthesis. In addition to the SNPs rs28470223 (C > T) in the promoter region of both HS3ST3A1 and rs62636623 (Gly/Arg) in the stem region of HS3ST3B1, three missense mutations (rs62056073, rs61729712 and rs9906590) located within the catalytic sulfotransferase domain of 3-OST-B1 are linked and associated to P. falciparum parasitaemia. To ascertain the functional effects of these SNP associations, we investigated the regulatory effect of rs28470223 and characterized the enzymatic activity of the missense SNP rs61729712 (Ser279Asn) localized at proximity of the substrate binding cleft...
April 28, 2018: Glycobiology
https://www.readbyqxmd.com/read/29688431/generation-and-characterization-of-a-site-specific-antibody-for-sirt1-o-glcnacylated-at-serine-549
#14
Hui Shan, Jiahui Sun, Minghui Shi, Xue Liu, Zhu Shi, Wengong Yu, Yuchao Gu
O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies thousands of proteins. However, the roles and mechanisms of O-GlcNAcylation have been clarified in only a few proteins, and one of the main reasons for this is the lack of site-specific anti-O-GlcNAc antibodies. Recently, we found that SIRT1, which is an NAD+-dependent deacetylase, is O-GlcNAcylated at the serine 549 site (S549) and plays a cytoprotective role under stress. However, the mechanism underlying the roles of SIRT1 O-GlcNAcylation remains unclear...
April 24, 2018: Glycobiology
https://www.readbyqxmd.com/read/29897456/%C3%AE-glucan-induced-cooperative-oligomerization-of-dectin-1-c-type-lectin-like-domain
#15
Hari P Dulal, Yoshiyuki Adachi, Naohito Ohno, Yoshiki Yamaguchi
Dectin-1 is a C-type lectin-like pattern recognition receptor that recognizes β(1-3)-glucans present on non-self pathogens. It is of great importance in innate immunity to understand the mechanism whereby Dectin-1 senses β(1-3)-glucans and induces intracellular signaling. In this study, we characterize the ligand binding and ligand-induced oligomerization of murine Dectin-1 using its C-type lectin-like domain (CTLD). Interaction of CTLD with laminarin, a β-glucan ligand, induced a tetramer of CTLD, as evidenced by size exclusion chromatography and multi-angle light scattering...
April 20, 2018: Glycobiology
https://www.readbyqxmd.com/read/29668902/distinct-amino-acid-residues-confer-one-of-three-udp-sugar-substrate-specificities-in-acinetobacter-baumannii-pglc-phosphoglycosyltransferases
#16
Christian M Harding, M Florencia Haurat, Evgeny Vinogradov, Mario F Feldman
Acinetobacter baumannii is an opportunistic human pathogen with the highest reported rates of multidrug resistance among Gram-negative pathogens. The capsular polysaccharide of A. baumannii is considered one of its most significant virulence factors providing resistance against complemented-mediated killing. Capsule synthesis in A. baumannii is usually initiated by the phosphoglycosyltransferase PglC. PglC transfers a phosphosugar from a nucleotide diphosphate-sugar to a polyprenol phosphate generating a polyprenol diphosphate-linked monosaccharide...
April 13, 2018: Glycobiology
https://www.readbyqxmd.com/read/29648596/unraveling-synthesis-of-the-cryptococcal-cell-wall-and-capsule
#17
Zhuo A Wang, Lucy X Li, Tamara L Doering
Fungal pathogens cause devastating infections in millions of individuals each year, representing a huge but underappreciated burden on human health. One of these, the opportunistic fungus Cryptococcus neoformans, kills hundreds of thousands of patients annually, disproportionately affecting people in resource-limited areas. This yeast is distinguished from other pathogenic fungi by a polysaccharide capsule that is displayed on the cell surface. The capsule consists of two complex polysaccharide polymers: a mannan substituted with xylose and glucuronic acid, and a galactan with galactomannan side chains that bear variable amounts of glucuronic acid and xylose...
April 10, 2018: Glycobiology
https://www.readbyqxmd.com/read/29688330/novel-thioglycoside-analogs-of-%C3%AE-galactosylceramide-stimulate-cytotoxicity-and-preferential-th1-cytokine-production-by-human-invariant-natural-killer-t-cells
#18
Ashanty M Melo, Lei Zhang, Éilis F Dockry, Andreea Petrasca, Yasmeen G Ghnewa, Eamon P Breen, Maria E Morrissey, Ciara O'Reilly, Robyn Bruen, Andrew O'Meara, Joanne Lysaght, Xiangming Zhu, Derek G Doherty
Invariant natural killer T (iNKT) cells recognize glycolipid antigens bound to CD1d molecules on antigen-presenting cells. Therapeutic activation of iNKT cells with the xenogeneic glycolipid α-galactosylceramide (α-GalCer) can prevent and reverse tumor growth in murine models, but clinical trials using α-GalCer-stimulated human iNKT cells have shown limited efficacy. We synthesized a series of thioglycoside analogs of α-GalCer with different substituents to the galactose residue and found that two of these compounds, XZ7 and XZ11, bound to CD1d-transfected HeLa cells and activated lines of expanded human iNKT cells...
April 6, 2018: Glycobiology
https://www.readbyqxmd.com/read/29618060/tn-and-stn-are-members-of-a-family-of-carbohydrate-tumor-antigens-that-possess-carbohydrate-carbohydrate-interactions
#19
Marit Sletmoen, Thomas A Gerken, Bjørn T Stokke, Joy Burchell, C Fred Brewer
The mucin-type O-glycome in cancer aberrantly expresses the truncated glycans Tn (GalNAcα1-Ser/Thr) and STn (Neu5Acα2,6GalNAcα1Ser/Thr). However, the role of Tn and STn in cancer and other diseases is not well understood. Our recent discovery of the self-binding properties (carbohydrate-carbohydrate interactions) of Tn (Tn - Tn) and STn (STn - STn) provides a model for their possible roles in cellular transformation. We also review evidence that Tn and STn are members of a larger family of glycan tumor antigens that possess carbohydrate-carbohydrate interactions, which may participate in oncogenesis...
April 3, 2018: Glycobiology
https://www.readbyqxmd.com/read/29596681/glycoengineering-design-options-for-igg1-in-cho-cells-using-precise-gene-editing
#20
Morten A Schulz, Weihua Tian, Yang Mao, Julie Van Coillie, Lingbo Sun, Joachim S Larsen, Yen-Hsi Chen, Claus Kristensen, Sergey Y Vakhrushev, Henrik Clausen, Zhang Yang
Precise gene editing technologies are providing new opportunities to stably engineer host cells for recombinant production of therapeutic glycoproteins with different glycan structures. The glycosylation of recombinant therapeutics has long been a focus for both quality and consistency of products and for optimizing and improving pharmacokinetic properties as well as bioactivity. Structures of glycans on therapeutic glycoproteins are important for circulation, biodistribution and bioactivity. In particular, the latter has been demonstrated for therapeutic IgG1 antibodies where the core α1,6Fucose on the conserved N-glycan at Asn297 have remarkable dampening effect on Fc effector functions...
March 27, 2018: Glycobiology
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