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Glycobiology

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https://www.readbyqxmd.com/read/29668902/distinct-amino-acid-residues-confer-one-of-three-udp-sugar-substrate-specificities-in-acinetobacter-baumannii-pglc-phosphoglycosyltransferases
#1
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
#2
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/29659839/airway-glycomic-and-allergic-inflammatory-consequences-resulting-from-keratan-sulfate-galactose-6-o-sulfotransferase-chst1-deficiency
#3
Tadahiro Kumagai, Takumi Kiwamoto, Mary E Brummet, Fan Wu, Kazuhiro Aoki, Zhou Zhu, Bruce S Bochner, Michael Tiemeyer
Siglec-F is a pro-apoptotic receptor on mouse eosinophils that recognizes 6'-sulfated sialyl Lewis X and 6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine structures on glycan arrays. We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation...
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
#4
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/29618064/subcellular-distribution-of-endogenous-malectin-under-rest-and-stress-conditions-is-regulated-by-ribophorin-i
#5
Qin-Peng Yang, Ming-Fen Fu, Hao Gao, Kazuo Yamamoto, Dan Hu, Sheng-Ying Qin
Malectin is a newly discovered endoplasmic reticulum (ER)-resident lectin, which specifically recognizes Glc2Man9GlcNAc2 on newly synthesized glycoproteins. We have previously demonstrated that malectin forms a complex with ribophorin I for selective retention of misfolded glycoproteins inside the cell. Here, we showed that ribophorin I also functions to regulate the subcellular localization of malectin under various conditions. Even though malectin does not contain an ER-retention signal motif, we found that endogenous malectin mainly localizes in the ER, which is disrupted upon suppression of ribophorin I, leading to its movement from ER to Golgi...
April 2, 2018: Glycobiology
https://www.readbyqxmd.com/read/29596681/glycoengineering-design-options-for-igg1-in-cho-cells-using-precise-gene-editing
#6
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
https://www.readbyqxmd.com/read/29635275/demystifying-o-glcnacylation-hints-from-peptide-substrates
#7
Jie Shi, Rob Ruijtenbeek, Roland J Pieters
O-GlcNAcylation, analogous to phosphorylation, is an essential post-translational modification of proteins at Ser/Thr residues with a single β-N-acetylglucosamine moiety. This dynamic protein modification regulates many fundamental cellular processes and its deregulation has been linked to chronic diseases such as cancer, diabetes and neurodegenerative disorders. Reversible attachment and removal of O-GlcNAc is governed only by O-GlcNAc transferase and O-GlcNAcase, respectively. Peptide substrates, derived from natural O-GlcNAcylation targets, function in the catalytic cores of these two enzymes by maintaining interactions between enzyme and substrate, which makes them ideal models for the study of O-GlcNAcylation and deglycosylation...
March 22, 2018: Glycobiology
https://www.readbyqxmd.com/read/29579213/global-aspects-of-viral-glycosylation-enveloped-viruses-herpesvirus-mass-spectrometry-mucin-type-o-glycosylation-viral-glycans
#8
Ieva Bagdonaite, Hans H Wandall
Enveloped viruses encompass some of the most common human pathogens causing infections of different severity, ranging from no or very few symptoms to lethal disease as seen with the viral hemorrhagic fevers. All enveloped viruses possess an envelope membrane derived from the host cell, modified with often heavily glycosylated virally encoded glycoproteins important for infectivity, viral particle formation, and immune evasion. While N-linked glycosylation of viral envelope proteins is well characterized with respect to location, structure, and site occupancy, information on mucin-type O-glycosylation of these proteins is less comprehensive...
March 22, 2018: Glycobiology
https://www.readbyqxmd.com/read/29579191/glycosyltransferase-genes-that-cause-monogenic-congenital-disorders-of-glycosylation-are-distinct-from-glycosyltransferase-genes-associated-with-complex-diseases
#9
Hiren J Joshi, Lars Hansen, Yoshiki Narimatsu, Hudson H Freeze, Bernard Henrissat, Eric Bennett, Hans H Wandall, Henrik Clausen, Katrine T Schjoldager
Glycosylation of proteins, lipids and proteoglycans in human cells involves at least 167 identified glycosyltransferases (GTfs), and these orchestrate the biosynthesis of diverse types of glycoconjugates and glycan structures. Mutations in this part of the genome-the GTf-genome-cause more than 58 rare, monogenic congenital disorders of glycosylation (CDGs). They are also statistically associated with a large number of complex phenotypes, diseases or predispositions to complex diseases based on Genome-Wide Association Studies (GWAS)...
March 22, 2018: Glycobiology
https://www.readbyqxmd.com/read/29562282/aanl-agrocybe-aegerita-lectin-2-is-a-new-facile-tool-to-probe-for-o-glcnacylation
#10
Wei Liu, Guanghui Han, Yalin Yin, Shuai Jiang, Guojun Yu, Qing Yang, Wenhui Yu, Xiangdong Ye, Yanting Su, Yajun Yang, Gerald W Hart, Hui Sun
O-linked N-acetylglucosamine (O-GlcNAcylation) is an important post-translational modification on serine or threonine of proteins, mainly observed in nucleus or cytoplasm. O-GlcNAcylation regulates many cell processes, including transcription, cell cycle, neural development, and nascent polypeptide chains stabilization. However, the facile identification of O-GlcNAc is a major bottleneck in O-GlcNAcylation research. Herein, we report that a lectin, AANL (Agrocybe aegerita GlcNAc specific lectin), also reported as AAL2, can be used as a powerful probe for O-GlcNAc identification...
March 19, 2018: Glycobiology
https://www.readbyqxmd.com/read/29562255/quantifying-the-binding-stoichiometry-and-affinity-of-histo-blood-group-antigen-oligosaccharides-for-human-noroviruses
#11
Ling Han, Ruixiang Zheng, Michele R Richards, Ming Tan, Elena N Kitova, Xi Jiang, John S Klassen
Human noroviruses (HuNoVs) are a major cause of acute gastroenteritis. Many HuNoVs recognize histo-blood group antigens (HBGAs) as cellular receptors or attachment factors for infection. It was recently proposed that HuNoV recognition of HBGAs involves a cooperative, multistep binding mechanism that exploits both known and, previously, unknown glycan binding sites. In this study, binding measurements, implemented using electrospray ionization mass spectrometry (ESI-MS), were performed on homodimers of the protruding domain (P dimers) of the capsid protein of three HuNoV strains [Saga (GII...
March 19, 2018: Glycobiology
https://www.readbyqxmd.com/read/29548035/specific-storage-of-glycoconjugates-with-terminal-%C3%AE-galactosyl-moieties-in-the-exocrine-pancreas-of-fabry-disease-patients-with-blood-group-b
#12
Jitka Rybová, Ladislav Kuchar, Helena Hulková, Befekadu Asfaw, Robert Dobrovolný, Jakub Sikora, Vladimír Havlícek, Ludovít Škultéty, Jana Ledvinová
Blood group B glycosphingolipids (B-GSLs) are substrates of the lysosomal alpha-galactosidase A (AGAL). Similar to its major substrate - globotriaosylceramide (Gb3Cer) - B-GSLs are not degraded and accumulate in the cells of patients affected by an inherited defect of AGAL activity (Fabry disease - FD).The pancreas is a secretory organ known to have high biosynthesis of blood group GSLs. Herein, we provide a comprehensive overview of the biochemical and structural abnormalities in pancreatic tissue from two male FD patients with blood group B...
March 14, 2018: Glycobiology
https://www.readbyqxmd.com/read/29548027/functional-crosstalk-among-oxidative-stress-and-o-glcnac-signaling-pathways-abstract
#13
Po-Han Chen, Jen-Tsan Chi, Michael Boyce
In metazoans, thousands of intracellular proteins are modified with O-linked β-N-acetylglucosamine (O-GlcNAc) in response to a wide range of stimuli and stresses. In particular, a complex and evolutionarily conserved interplay between O-GlcNAcylation and oxidative stress has emerged in recent years. Here, we review the current literature on the connections between O-GlcNAc and oxidative stress, with a particular emphasis on major signaling pathways, such as KEAP1/NRF2, FOXO, NFκB, p53 and cell metabolism...
March 14, 2018: Glycobiology
https://www.readbyqxmd.com/read/29546349/cancer-glycan-epitopes-biosynthesis-structure-and-function
#14
Oliver M Pearce
Aberrant glycan epitopes are a classic hallmark of malignant transformation, yet their full clinical potential in cancer diagnostics and therapeutics is yet to be realized. This is partly because our understanding of how these epitopes are regulated remains poorly understood. In this review cancer glycan epitopes for the major glycan classes are summarized with a focus on their biosynthesis, structure, and role in cancer progression. Their application as cancer biomarkers, in particular the more recent work on cancer glycoforms, and the advantages these offer over the glycan or protein alone are discussed...
March 13, 2018: Glycobiology
https://www.readbyqxmd.com/read/29522135/sulfated-fucans-and-a-sulfated-galactan-from-sea-urchins-as-potent-inhibitors-of-selectin-dependent-hematogenous-metastasis
#15
Felipe C O B Teixeira, Eliene Oliveira Kozlowski, Kayene Vitória de A Micheli, Ana Cristina E S Vilela-Silva, Lubor Borsig, Mauro S G Pavão
Metastasis is responsible for the majority of cancer-associated deaths, though only a very small number of tumor cells are able to efficiently complete all the steps of that process. Tumor cell survival in the bloodstream is one of the limiting aspects of the metastatic cascade. The formation of tumor cell-platelet complexes that promote tumor cell survival is facilitated by the binding of P-selectin on activated platelets to sialyl Lewis-containing oligosaccharides on the surface of tumor cells. Inhibition of this interaction has been shown to attenuate metastasis...
March 7, 2018: Glycobiology
https://www.readbyqxmd.com/read/29518231/understanding-the-glycome-an-interactive-view-of-glycosylation-from-glycocompositions-to-glycoepitopes
#16
Davide Alocci, Marie Ghraichy, Elena Barletta, Alessandra Gastaldello, Julien Mariethoz, Frederique Lisacek
Nowadays, due to the advance of experimental techniques in glycomics, large collections of glycan profiles are regularly published. The rapid growth of available glycan data accentuates the lack of innovative tools for visualizing and exploring large amount of information. Scientists resort to using general-purpose spreadsheet applications to create ad hoc data visualization. Thus, results end up being encoded in publication images and text, while valuable curated data is stored in tables and published as supplemental material...
March 6, 2018: Glycobiology
https://www.readbyqxmd.com/read/29506202/applications-of-a-highly-%C3%AE-2-6-selective-pseudosialidase
#17
Peter Both, Michel Riese, Christopher J Gray, Kun Huang, Edward G Pallister, Iaroslav Kosov, Louis P Conway, Josef Voglmeir, Sabine L Flitsch
Within human biology, combinations of regioisomeric motifs of α2,6- or α2,3-sialic acids linked to galactose are frequently observed attached to glycoconjugates. These include glycoproteins and glycolipids, with each linkage carrying distinct biological information and function. Microbial linkage-specific sialidases have become important tools for studying the role of these sialosides in complex biological settings, as well as being used as biocatalysts for glycoengineering. However, currently, there is no α2,6-specific sialidase available...
February 28, 2018: Glycobiology
https://www.readbyqxmd.com/read/29471321/overexpression-of-heparanase-in-mice-promoted-megakaryopoiesis
#18
Ying-Xia Tan, Hao Cui, Lu-Ming Wan, Feng Gong, Xiao Zhang, Israel Vlodavsky, Jin-Ping Li
Heparanase, an endo-glucuronidase that specifically cleaves heparan sulfate, is upregulated in several pathological conditions. In this study, we aimed to find a correlation of heparanase expression and platelets production. In the transgenic mice overexpressing human heparanase (Hpa-tg), hematological analysis of blood samples revealed a significantly higher number of platelets in comparison with wild-type (Ctr) mice, while no significant difference was found in leukocytes and red blood cell number between the two groups...
February 19, 2018: Glycobiology
https://www.readbyqxmd.com/read/29452367/variant-in-human-pofut1-reduces-enzymatic-activity-and-likely-causes-a-recessive-microcephaly-global-developmental-delay-with-cardiac-and-vascular-features
#19
Hideyuki Takeuchi, Derek Wong, Michael Schneider, Hudson H Freeze, Megumi Takeuchi, Steven J Berardinelli, Atsuko Ito, Hane Lee, Stanley F Nelson, Robert S Haltiwanger
Protein O-fucosyltransferase-1 (POFUT1) adds O-fucose monosaccharides to epidermal growth factor-like (EGF) repeats found on approximately 100 mammalian proteins, including Notch receptors. Haploinsufficiency of POFUT1 has been linked to adult-onset Dowling Degos Disease (DDD) with hyperpigmentation defects. Homozygous deletion of mouse Pofut1 results in embryonic lethality with severe Notch-like phenotypes including defects in somitogenesis, cardiogenesis, vasculogenesis, and neurogenesis, but the extent to which POFUT1 is required for normal human development is not yet understood...
February 14, 2018: Glycobiology
https://www.readbyqxmd.com/read/29390163/identification-of-internally-sialylated-carbohydrate-tumor-marker-candidates-including-sda-cad-antigens-by-focused-glycomic-analyses-utilizing-the-substrate-specificity-of-neuraminidase
#20
Miki Tanaka-Okamoto, Ken Hanzawa, Mikio Mukai, Hidenori Takahashi, Masayuki Ohue, Yasuhide Miyamoto
In our previous study, 14 sulfated carbohydrate tumor marker candidates were identified by focused glycomic analyses. Here, glycomic analyses focused on internally sialylated glycans to identify novel marker candidates. Internally sialylated glycans were enriched by digestion of pyridylaminated glycans prepared from sera withα-neuraminidase from Salmonella typhimurium, which did not cleave sialic acids linked to internal residues, followed by anion-exchange chromatography. Next, internally sialylated O-glycan profiles were constructed using two types of high performance liquid chromatography, which were compared between 20 healthy controls and 11 patients with gastric cancer and 9 patients with pancreatic cancer...
January 30, 2018: Glycobiology
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