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Tomoharu Takeuchi, Mayumi Tamura, Kenji Ishiwata, Megumi Hamasaki, Shinjiro Hamano, Yoichiro Arata, Tomomi Hatanaka
Galactoseβ1-4Fucose (GalFuc) is a unique disaccharide found in invertebrates including nematodes. A fungal galectin CGL2 suppresses nematode development by recognizing the galactoseβ1-4fucose epitope. The Caenorhabditis elegans galectin LEC-6 recognizes it as an endogenous ligand and the Glu67 residue of LEC-6 is responsible for this interaction. We found that mammalian galectin-2 (Gal-2) also has a comparable glutamate residue, Glu52. In the present study, we investigated the potential nematode-suppressing activity of Gal-2 using C...
March 15, 2019: Glycobiology
Kathya Gutiérrez-Huante, Roberta Salinas-Marín, Héctor M Mora Montes, Ramón A Gonzalez, Iván Martínez-Duncker
Certain viral infections are known to modify the glycosylation profile of infected cells through the overexpression of specific host cell fucosyltransferases (FUTs). Infection with CMV (cytomegalovirus), HCV (hepatitis C virus), HSV-1 (herpes simplex virus type-1) and VZV (varicella-zoster virus) increase the expression of fucosylated epitopes, including antigens sLex (Siaα2-3 Galβ1-4(Fucα1-3)GlcNAcβ1-R) and Ley (Fucα1-2 Galβ1-4(Fucα1-3)GlcNAcβ1-R). The reorganization of the glycocalyx induced by viral infection may favor the spread of viral progeny, and alter diverse biological functions mediated by glycans, including recognition by the adaptive immune system...
March 14, 2019: Glycobiology
Emil Tykesson, Marco Maccarana, Hanna Thorsson, Jian Liu, Anders Malmström, Ulf Ellervik, Gunilla Westergren-Thorsson
The glycosaminoglycan dermatan sulfate (DS) is a well-known activator of heparin cofactor II-dependent inactivation of thrombin. In contrast to heparin, dermatan sulfate has never been prepared recombinantly from material of non-animal origin. Here we report on the enzymatic synthesis of structurally well-defined DS with high anticoagulant activity. Using a microbial K4 polysaccharide and the recombinant enzymes DS-epimerase 1, dermatan 4-O-sulfotransferase 1, uronyl 2-O-sulfotransferase and N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase, several new glycostructures have been prepared, such as a homogenously sulfated IdoA-GalNAc-4S polymer and its 2-O-, 6-O- and 2,6-O-sulfated derivatives...
March 14, 2019: Glycobiology
Eriko Nakato, Xin Liu, Inger Eriksson, Maki Yamamoto, Akiko Kinoshita-Toyoda, Hidenao Toyoda, Lena Kjellén, Jin-Ping Li, Hiroshi Nakato
A class of carbohydrate-modified proteins, heparan sulfate proteoglycans (HSPGs), play critical roles both in normal development and during disease. Genetic studies using a model organism, Drosophila, have been contributing to understanding the in vivo functions of HSPGs. Despite the many strengths of the Drosophila model for in vivo studies, biochemical analysis of Drosophila HS is somewhat limited, mainly due to the insufficient amount of the material obtained from the animal. To overcome this obstacle, we generated mutant cell lines for four HS modifying enzymes that are critical for the formation of ligand binding sites on HS, Hsepi, Hs2st, Hs6st, and Sulf1, using a recently established method...
March 14, 2019: Glycobiology
Pravinkumar Choudhary, Rupa Nagar, Vaidhvi Singh, Aadil Hussain Bhat, Yogita Sharma, Alka Rao
Knowledge of glycosylation status and glycan-pattern of proteins are of considerable medical, academic and application interest. ProGlycProt V2.0 ( therefore, is conceived and maintained as an exclusive web-resource providing comprehensive information on experimentally validated glycoproteins and protein glycosyltransferases (GTs) of prokaryotic origin. The second release of ProGlycProt V2.0 features a major update with a 191 % increase in the total number of entries, manually collected and curated from 607 peer-reviewed publications on the subject...
March 5, 2019: Glycobiology
Stella Tamana, Vasilis J Promponas
Despite the controversy regarding the importance of protein N-linked glycosylation in species of the genus Plasmodium, genes potentially encoding core subunits of the oligosaccharyltransferase (OST) complex have already been characterized in completely sequenced genomes of malaria parasites. Nevertheless, the currently established notion is that only four out of eight subunits of the OST complex-which is considered conserved across eukaryotes-are present in Plasmodium species. In this study, we carefully conduct computational analysis to provide unequivocal evidence that all components of the OST complex, with the exception of Swp1/Ribophorin II, can be reliably identified within completely sequenced plasmodial genomes...
March 5, 2019: Glycobiology
Anita Ghosh, Aditi Banerjee, L Mario Amzel, Gerardo R Vasta, Mario A Bianchet
Galectins, highly conserved β-galactoside-binding lectins, have diverse regulatory roles in development and immune homeostasis and can mediate protective functions during microbial infection. In recent years, the role of galectins in viral infection has generated considerable interest. Studies on highly pathogenic viruses have provided invaluable insight into the participation of galectins in various stages of viral infection, including attachment and entry. Detailed mechanistic and structural aspects of these processes remain undetermined...
March 5, 2019: Glycobiology
Zeba Siddiqui, Mohammad Faisal, Abdul Rahman Alatar, Saheem Ahmad
Glycation of biological macromolecules, due to hyperglycemia, promotes the formation of advanced glycation end products (AGEs). It is accelerated in diabetic patients and is responsible for the pathophysiology and progression of diabetes. Previous reports have shown that amount of AGEs formation and glycation-induced structural damage is higher in hemoglobin (Hb) than other proteins present in blood. In our previous study, we have shown structural changes in Hb by D-ribose which may result into the generation of immunogenic neo-epitopes...
March 5, 2019: Glycobiology
Danyang Li, Somshuvra Mukhopadhyay
SLC35A2 transports UDP-galactose from the cytosol to the lumen of the Golgi apparatus and endoplasmic reticulum for glycosylation. Mutations in SLC35A2 induce a congenital disorder of glycosylation. Despite the biomedical relevance, mechanisms of transport via SLC35A2 and the impact of disease-associated mutations on activity are unclear. To address these issues, we generated a predicted structure of SLC35A2 and assayed for the effects of a set of structural and disease-associated mutations. Activity assays were performed using a rescue approach in ΔSLC35A2 cells and took advantage of the fact that SLC35A2 is required for expression of the glycosphingolipid globotriaosylceramide (Gb3), the cell surface receptor for Shiga toxin 1 (STx1) and 2 (STx2)...
March 5, 2019: Glycobiology
Hyun-Kyu Choi, Dongheon Lee, Akshi Singla, Joseph Sang-Il Kwon, Hung-Jen Wu
We recently discovered that the nature of lectin multivalency and glycolipid diffusion on cell membranes could lead to the heteromultivalent binding (i.e., a single lectin simultaneously binding to different types of glycolipid ligands). This heteromultivalent binding may even govern the lectin-glycan recognition process. To investigate this, we developed the kinetic Monte Carlo simulation, which only considers the fundamental physics/chemistry principles, to model the process of lectin binding to glycans on cell surfaces...
March 2, 2019: Glycobiology
Andrea Persson, Jonas Nilsson, Egor Vorontsov, Fredrik Noborn, Göran Larson
It is generally accepted that the biosynthesis of chondroitin sulfate and heparan sulfate is proceeding from a common linkage region tetrasaccharide comprising GlcA-Gal-Gal-Xyl-O-. The linkage region can undergo various modifications such as sulfation, phosphorylation, and sialylation, and as the methods for studying glycosaminoglycan structure have been developed and refined, the number of discovered modifications has increased. Previous studies on the linkage region and the glycosyltransferases involved in the biosynthesis suggest that variants of the linkage region tetrasaccharide may also be possible...
March 2, 2019: Glycobiology
Matthew P Campbell, Jodie L Abrahams, Erdmann Rapp, Weston B Struwe, Catherine E Costello, Milos Novotny, Rene Ranzinger, William S York, Daniel Kolarich, Pauline M Rudd, Carsten Kettner
The Minimum Information Required for A Glycomics Experiment (MIRAGE) is an initiative created by experts in the fields of glycobiology, glycoanalytics and glycoinformatics to design guidelines that improve the reporting and reproducibility of glycoanalytical methods. Previously, the MIRAGE Commission has published guidelines for describing sample preparation methods and the reporting of glycan array and mass spectrometry techniques and data collections. Here, we present the first version of guidelines that aim to improve the quality of the reporting of liquid chromatography (LC) glycan data in the scientific literature...
February 19, 2019: Glycobiology
Catharina Steentoft, Max Fuhrmann, Federico Battisti, Julie Van Coillie, Thomas D Madsen, Diana Campos, Adnan Halim, Sergey Y Vakhrushev, Hiren Joshi, Hans Schreiber, Ulla Mandel, Yoshiki Narimatsu
Successful application of potent antibody-based T-cell engaging immunotherapeutic strategies is currently limited mainly to hematological cancers. One major reason is the lack of well-characterized antigens on solid tumors with sufficient cancer specific expression. Aberrantly O-glycosylated proteins contain promising cancer-specific O-glycopeptide epitopes suitable for immunotherapeutic applications, but currently only few examples of such antibody epitopes have been identified. We previously showed that chimeric antigen receptor T-cells directed towards aberrantly O-glycosylated MUC1 can control malignant growth in a mouse model...
February 6, 2019: Glycobiology
Ksenia S Egorova, Yuriy A Knirel, Philip V Toukach
In 2017, we reported a new database on glycosyltransferase (GT) activities, CSDB_GT (, which was built at the platform of the Carbohydrate Structure Database (CSDB, and contained data on experimentally confirmed GT activities from Arabidopsis thaliana. All entries in CSDB_GT are curated manually upon the analysis of scientific publications, and the key features of the database are accurate structural, genetic, protein and bibliographic references and close-to-complete coverage on experimentally proven GT activities in selected species...
January 31, 2019: Glycobiology
Tyler J Stewart, Kazuo Takahashi, Robert H Whitaker, Milan Raska, William J Placzek, Jan Novak, Matthew B Renfrow
GalNAc-type O-glycans are often added to proteins post-translationally in a clustered manner in repeat regions of proteins, such as mucins and IgA1. Observed IgA1 glycosylation patterns show that glycans occur at similar sites with similar structures. It is not clear how the sites and number of glycans added to IgA1, or other proteins, can follow a conservative process. GalNAc-transferases initiate GalNAc-type glycosylation. In IgA nephropathy, an autoimmune disease, the sites and O-glycan structures of IgA1 hinge-region are altered, giving rise to a glycan autoantigen...
January 31, 2019: Glycobiology
Dongmei Zhang, Qing Xie, Yanping Wang, Jinsheng Miao, Ling Li, Tong Zhang, Xiufeng Cao, Yunsen Li
Aberrant glycosylation is strongly correlated with the development of various cancers. Tumor-associated carbohydrate antigens, including N-glycans, are predominantly expressed on the tumor cell surface. Because the incidence of colorectal cancer is high in China, we investigated aberrant N-glycans from colorectal cancer tissues (CRC) in Chinese patients. By Linear ion trap quadrupole-electrospray ionization mass spectrometry (LTQ-ESI-MS), we performed glycomic assays on N-glycans obtained from solid colorectal cancer tissues and paired peritumoral tissues...
January 30, 2019: Glycobiology
Anne-Mari Mustonen, Anu Salvén, Vesa Kärjä, Kirsi Rilla, Johanna Matilainen, Petteri Nieminen
Non-alcoholic fatty liver disease is among the most common liver diseases worldwide and one cause of cirrhosis that can result in the development of hepatocellular carcinoma (HCC). Hyaluronan (HA) is a high-molecular-mass glycosaminoglycan with diverse functions in tissue injury and repair, for instance, in inflammation and fibrogenesis. The aim of the present study was to investigate the relationships between the HA synthesizing and degrading enzymes in a spectrum of liver pathologies. This was realized by histological staining of liver sections from controls and patients with simple steatosis, steatohepatitis, cirrhosis, and HCC (n = 90)...
January 25, 2019: Glycobiology
Tanja Višnjar, Rok Romih, Daša Zupancic
Urinary bladder cancer is the ninth most common cancer in developed countries with poor prognosis and outcome for the patient due to the challenging diagnosis and limited treatment possibilities. Bladder cancer arises mainly from urothelial cells lining the lumen. Urothelial cells form a three- to five-layered urothelium, which maintains the blood-urine barrier. The carbohydrates that cover the apical surface of superficial urothelial cells, i.e., umbrella cells, are crucial for this function. The composition of the carbohydrate covering is altered during urothelial cancer transformation...
January 25, 2019: Glycobiology
Sang-Jun Park, Jumin Lee, Yifei Qi, Nathan R Kern, Hui Sun Lee, Sunhwan Jo, InSuk Joung, Keehyung Joo, Jooyoung Lee, Wonpil Im
Characterizing glycans and glycoconjugates in the context of three-dimensional structures is important in understanding their biological roles and developing efficient therapeutic agents. Computational modeling and molecular simulation have become an essential tool complementary to experimental methods. Here, we present a computational tool, Glycan Modeler for in silico N-/O-glycosylation of the target protein and generation of carbohydrate-only systems. In our previous study, we developed Glycan Reader, a web-based tool for detecting carbohydrate molecules from a PDB structure and generation of simulation system and input files...
January 25, 2019: Glycobiology
M Osman Sheikh, Elisabet Gas-Pascual, John N Glushka, Juan M Bustamante, Lance Wells, Christopher M West
Trypanosoma cruzi is a protozoan parasite that causes Chagas disease, a debilitating condition that affectsover 10 million humans in the American continents. In addition to its traditional mode of human entry via the 'kissing bug' in endemic areas, the infection can also be spread in non-endemic countries through blood transfusion, organ transplantation, eating food contaminated with the parasites, and from mother to fetus. Previous NMR-based studies established that the parasite expresses a variety of strain-specific and developmentally-regulated O-glycans that may contribute to virulence...
January 12, 2019: Glycobiology
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