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Glycobiology.
IRL Press at Oxford University Press,
Glycobiology.

IRL Press at Oxford University Press,

0959-6658

Glycobiology./Journal Glycobiology.
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    Meeting report on 14(th) Jenner Glycobiology and Medicine Symposium: glycobiology in immunology, medicine, and clinical practice

    O'Flaherty, RoisinOpdenakker, GhislainClausen, HenrikGerardy-Schahn, Rita...
    2页
      原文链接:
    • NSTL
    • Oxford Univ Press

    Carbohydrate Structure Database oligosaccharide conformation tool

    Scherbinina, Sofya, IFrank, MartinToukach, Philip, V
    9页
    查看更多>>摘要：Population analysis in terms of glycosidic torsion angles is frequently used to reveal preferred conformers of glycans. However, due to high structural diversity and flexibility of carbohydrates, conformational characterization of complex glycans can be a challenging task. Herein, we present a conformation module of oligosaccharide fragments occurring in natural glycan structures developed on the platform of the Carbohydrate Structure Database. Currently, this module deposits free energy surface and conformer abundance maps plotted as a function of glycosidic torsions for 194 "inter" residue bonds. Data are automatically and continuously derived from explicit-solvent molecular dynamics (MD) simulations. The module was also supplemented with high-temperature MD data of saccharides (2,403 maps) provided by GlycoMapsDB (hosted by GLYCOSCIENCES.de project). Conformational data defined by up to 4 torsional degrees of freedom can be freely explored using a web interface of the module available at http://csdb.glycoscience.ru/database/core/search_conf.html. [GRAPHICS] .
      原文链接:
    • NSTL
    • Oxford Univ Press

    N-glycan profiles of acute myocardial infarction patients reveal potential biomarkers for diagnosis, severity assessment, and treatment monitoring

    Lim, Si YingHendra, ChristopherYeo, Xin HaoTan, Xin Yi...
    14页
    查看更多>>摘要：Acute myocardial infarction (AMI) is a leading cause of mortality and morbidity worldwide. Diagnostic challenges remain in this highly time-sensitive condition. Using capillary electrophoresis-laser-induced fluorescence, we analyzed the blood plasma N-glycan profile in a cohort study comprising 103 patients with AMI and 69 controls. Subsequently, the data generated was subjected to classification modeling to identify potential AMI biomarkers. An area under the Receiving Operating Characteristic curve (AUC(ROC)) of 0.81 was obtained when discriminating AMI versus non-MI patients. We postulate that the glycan profile involves a switch from a pro- to an anti-inflammatory state in the AMI pathophysiology. This was supported by significantly decreased levels in galactosylation, alongside increased levels in sialylation, afucosylation, and GlcNAc bisection levels in the blood plasma of AMI patients. By substantiating the glycomics analysis with immunoglobulin G (IgG) protein measurements, robustness of the glycan-based classifiers was demonstrated. Changes in AMI-related IgG activities were also confirmed to be associated with alterations at the glycosylation level. Additionally, a glycan-biomarker panel (GBP) derived from glycan features and current clinical biomarkers performed remarkably (AUC(ROC) = 0.90, sensitivity = 0.579 at 5 percent false positive rate) when discriminating between patients with ST-segment elevation MI (n = 84) and non-ST-segment elevation MI (n = 19). Moreover, by applying the model trained using glycomics information, AMI and controls can still be discriminated at one and six months after baseline. Thus, glycomics biomarkers could potentially serve as a valuable complementary test to current diagnostic biomarkers. Additional research on their utility and associated biomechanisms via a large-scale study is recommended.
      原文链接:
    • NSTL
    • Oxford Univ Press

    Structural characterization of human milk oligosaccharides using ultrahigh performance liquid chromatography-helium charge transfer dissociation mass spectrometry

    Mendis, Praneeth M.Jackson, Glen P.
    13页
    查看更多>>摘要：The combination of helium charge transfer dissociation mass spectrometry (He-CTD-MS) with ultrahigh performance liquid chromatography (UHPLC) is presented for the analysis of a complex mixture of acidic and neutral human milk oligosaccharides (HMOs). The research focuses on the identification of the monosaccharide sequence, the branching patterns, the sialylation/fucosylation arrangements, and the differentiation of isomeric oligosaccharides in the mixture. Initial studies first optimized the conditions for the UHPLC separation and the He-CTD-MS conditions. Results demonstrate that He-CTD is compatible with UHPLC timescales and provides unambiguous glycosidic and cross-ring cleavages from both the reducing and the nonreducing ends, which is not typically possible using collision-induced dissociation. He-CTD produces informative fragments, including (0,3)A(n) and (0,4)A(n) ions, which have been observed with electron transfer dissociation, electron detachment dissociation, and ultraviolet photodissociation (UVPD) and are crucial for differentiating the alpha-2,3- versus alpha-2,6-linked sialic acid (Neu5Ac) residues present among sialyllacto-N-tetraose HMOs. In addition to the linkage positions, He-CTD is able to differentiate structural isomers for both sialyllacto-N-tetraoses and lacto-N-fucopentaoses structures by providing unique, unambiguous cross-ring cleavages of types (0,2)A(n), X-0,2(n), and (1,5)A(n) while preserving most of the labile Neu5Ac and fucose groups.
      原文链接:
    • NSTL
    • Oxford Univ Press

    Recombinant norovirus capsid protein VP1 (GII.4) expressed in H5 insect cells exhibits post-translational modifications with potential impact on lectin activity and vaccine design

    Hanisch, Franz-Georg
    10页
    查看更多>>摘要：Although surface proteins of most enveloped viruses are glycosylated, among non-enveloped viruses only few express glycoproteins in their capsid as infective virions. Noroviruses belong to the latter group and are known to express one major capsid protein (VP1) that lacks genuine glycosylation. In the context of vaccine development based on VLPs and in searches for food additives offering potential prophylactic or therapeutic applications an increasing number of reports refers to the use of virus-like particles (VLPs) that were produced as secretory products in insect cells. We asked the question whether recombinant VLPs (GII.4 Sydney, 2012) produced via the baculovirus vector in H5 insect cells may be glycosylated in the protruding domains that are involved in receptor binding and immune reactivity. Mass spectrometric analysis of tryptic VP1 peptides prior to and after beta-elimination Michael addition in 70% ethylamine revealed Thr238, and Ser519 in the P1 domain, and Thr350, Thr369, Thr371, and Thr381 in the P2 domain as modified. Thr65, Ser67, and Thr350 were revealed by liquid chromatography-mass spectrometry to carry HexNAc or Hex-HexNAc modifications, respectively. Monosaccharide analysis by gas chromatography-mass spectrometry confirmed the presence of GlcNAc on VLP protein, whereas immunoassays with lectins and antibodies demonstrated O-linked GlcNAc on VP1 protein. Post-translational modifications of virus capsid proteins may contribute to a modulation of immunodominant surface epitopes and need to be considered in anti-norovirus vaccine design. Some modifications are located near amino acid side chains involved in the binding of blood group active sugar receptors.
      原文链接:
    • NSTL
    • Oxford Univ Press

    Lack of N-glycosylation increases amyloidogenic processing of the amyloid precursor protein

    Lin, Tongvan Husen, Lea S.Yu, YangTjernberg, Lars O....
    12页
    查看更多>>摘要：The amyloid precursor protein (APP) is a ubiquitously expressed type 1 transmembrane protein mostly known for serving as a precursor to the amyloid-beta peptide (A beta), a culprit in Alzheimer disease (AD). However, APP also has important physiological functions by being implicated in, for instance, adhesion, signaling, neuronal development, and synaptic function. Human APP contains 2 N-glycosylation sites, at asparagine (N) 467 (N467) and N496. Here, we studied the role of N-glycosylation on APP trafficking and processing by constructing APP-SNAP plasmid vectors for wildtype APP and N-glycosylation site mutants in which N467 or N496 was replaced by glutamine (Q) and expressed these in HEK293T cells. Lack of either of the 2 N-glycans resulted in a reduction in the size of intracellular APP-SNAP-positive vesicles and a reduction of APP-SNAP in the plasma membrane and lysosomes. Importantly, loss of either of the 2 N-glycans resulted in elevated levels of intracellular as well as secreted A beta 42. These data suggest that N-glycans have a major impact on trafficking and processing of APP and could play an important role in the development of AD.
      原文链接:
    • NSTL
    • Oxford Univ Press

    A dominant negative splice variant of the heparan sulfate biosynthesis enzyme NDST1 reduces heparan sulfate sulfation

    Missaghian, ParisaDierker, TabeaKhosrowabadi, ElhamAxling, Fredrik...
    11页
    查看更多>>摘要：NDST1 (glucosaminyl N-deacetylase/N-sulfotransferase) is a key enzyme in heparan sulfate (HS) biosynthesis, where it is responsible for HS N-deacetylation and N-sulfation. In addition to the full length human enzyme of 882 amino acids, here designated NDST1A, a shorter form containing 825 amino acids (NDST1B) is synthesized after alternative splicing of the NDST1 mRNA. NDST1B is mostly expressed at a low level, but increased amounts are seen in several types of cancer where it is associated with shorter survival. In this study, we aimed at characterizing the enzymatic properties of NDST1B and its effect on HS biosynthesis. Purified recombinant NDST1B lacked both N-deacetylase and N-sulfotransferase activities. Interestingly, HEK293 cells overexpressing NDST1B synthesized HS with reduced sulfation and altered domain structure. Fluorescence resonance energy transfer-microscopy demonstrated that both NDST1A and NDST1B had the capacity to interact with the HS copolymerase subunits EXT1 and EXT2 and also to form NDST1A/NDST1B dimers. Since lysates from cells overexpressing NDST1B contained less NDST enzyme activity than control cells, we suggest that NDST1B works in a dominant negative manner, tentatively by replacing the active endogenous NDST1 in the enzyme complexes taking part in biosynthesis.
      原文链接:
    • NSTL
    • Oxford Univ Press

    Characterization of five marine family 29 glycoside hydrolases reveals an alpha-L-fucosidase targeting specifically Fuc(alpha 1,4)GlcNAc

    Schultz-Johansen, MikkelStougaard, PeterSvensson, BirteTeze, David...
    11页
    查看更多>>摘要：L-Fucose is the most widely distributed L-hexose in marine and terrestrial environments and presents a variety of functional roles. L-Fucose is the major monosaccharide in the polysaccharide fucoidan from cell walls of brown algae and is found in human milk oligosaccharides (HMOs) and the Lewis blood group system, where it is important in cell signaling and immune response stimulation. Removal of fucose from these biomolecules is catalyzed by fucosidases belonging to different carbohydrate-active enzyme (CAZy) families. Fucosidases of glycoside hydrolase family 29 (GH29) release alpha-L-fucose from non-reducing ends of glycans and display activities targeting different substrate compositions and linkage types. While several GH29 fucosidases from terrestrial environments have been characterized, much less is known about marine members of GH29 and their substrate specificities, as only four marine GH29 enzymes were previously characterized. Here, five GH29 fucosidases originating from an uncultured fucoidandegrading marine bacterium (Paraglaciecola sp.) were cloned and produced recombinantly in Escherichia coli. All five enzymes (Fp231, Fp239, Fp240, Fp251 and Fp284) hydrolyzed the synthetic substrate CNP-alpha-L-fucose. Assayed against up to 17 fucose-containing oligosaccharides, Fp239 showed activity against the Lewis Y antigen, 2'- and 3-fucosyllactose, while Fp284 degraded 2'-fucosyllactose and Fuc(alpha 1,6)GlcNAc. Furthermore, Fp231 displayed strict specificity against Fuc(alpha 1,4)GlcNAc, a previously unreported specificity in GH29. Fp231 is a monomeric enzyme with pH and temperature optima at pH 5.6-6.0 and 25 degrees C, hydrolyzing Fuc(alpha 1,4)GlcNAc with k(cat) = 1.3 s(-1) and K-m = 660 mu M. Altogether, the findings extend our knowledge about GH29 family members from the marine environment, which are so far largely unexplored.
      原文链接:
    • NSTL
    • Oxford Univ Press

    Growth of Bifidobacterium pseudocatenulatum in medium containing N-acetylsucrosamine: enzyme that induces the growth of this bacterium via degradation of this disaccharide

    Nagashima, MakotoNakamura, HirokiHosaka, HirokiHirano, Takako...
    10页
    查看更多>>摘要：Bifidobacterium pseudocatenulatum grows well in the early stages of cultivation in medium containing sucrose (Suc), whereas its growth in medium containing the analogue disaccharide N-acetylsucrosamine (SucNAc) tends to exhibit a considerable delay. To elucidate the cause of this phenomenon, we investigated the proliferation pattern of B. pseudocatenulatum in medium containing D-glucose (Glc) and SucNAc and identified the enzyme that degrades this disaccharide. We found that B. pseudocatenulatum initially proliferates by assimilating Glc, with subsequent growth based on SucNAc assimilation depending on production of the beta-fructofuranosidase, which can hydrolyze SucNAc, after Glc is completely consumed. Thus, B. pseudocatenulatum exhibited a diauxic growth pattern in medium containing Glc and SucNAc. In contrast, when cultured in medium containing Glc and Suc, B. pseudocatenulatum initially grew by degrading Suc via the phosphorolysis activity of Suc phosphorylase, which did not react to SucNAc. These observations indicate that B. pseudocatenulatum proliferates by assimilating Suc and SucNAc via different pathways. The beta-fructofuranosidase of B. pseudocatenulatum exhibited higher hydrolytic activity against several naturally occurring Suc-based tri- or tetrasaccharides than against Suc, suggesting that this enzyme actively catabolizes oligosaccharides other than Suc.
      原文链接:
    • NSTL
    • Oxford Univ Press