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https://www.readbyqxmd.com/read/27914091/toward-clinical-use-of-the-igg-specific-enzymes-ides-and-endos-against-antibody-mediated-diseases
#1
Mattias Collin, Lars Björck
The endoglycosidase EndoS and the protease IdeS from the human pathogen Streptococcus pyogenes are immunomodulating enzymes hydrolyzing human IgG. IdeS cleaves IgG in the lower hinge region, while EndoS hydrolyzes the conserved N-linked glycan in the Fc region. Both enzymes are remarkably specific for human IgG that after hydrolysis loses most of its effector functions, such as binding to leukocytes and complement activation, all contributing to bacterial evasion of adaptive immunity. However, taken out of their infectious context, we and others have shown that IdeS and EndoS can alleviate autoimmune disease in a number of animal models of antibody-mediated disorders...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27909778/it-is-all-about-the-solvent-on-the-importance-of-the-mobile-phase-for-zic-hilic-glycopeptide-enrichment
#2
Kathirvel Alagesan, Sana Khan Khilji, Daniel Kolarich
Glycopeptide enrichment is a crucial step in glycoproteomics for which hydrophilic interaction chromatography (HILIC) has extensively been applied due to its low bias towards different glycan types. A systematic evaluation of applicable HILIC mobile phases on glycopeptide enrichment efficiency and selectivity is, to date, however, still lacking. Here, we present a novel, simplified technique for HILIC enrichment termed "Drop-HILIC", which was applied to systematically evaluate the mobile phase effect on ZIC-HILIC (zwitterionic type of hydrophilic interaction chromatography) glycopeptide enrichment...
December 1, 2016: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/27908641/free-energy-perturbation-calculation-of-relative-binding-free-energy-between-broadly-neutralizing-antibodies-and-the-gp120-glycoprotein-of-hiv-1
#3
Anthony J Clark, Tatyana Gindin, Baoshan Zhang, Lingle Wang, Robert Abel, Colleen S Murret, Fang Xu, Amy Bao, Nina J Lu, Tongqing Zhou, Peter D Kwong, Lawrence Shapiro, Barry Honig, Richard A Friesner
Direct calculation of relative binding affinities between antibodies and antigens is a long-sought goal. However, despite substantial efforts, no generally applicable computational method has been described. Here we describe a systematic free energy perturbation (FEP) protocol and calculate the binding affinities between the gp120 envelope glycoprotein of HIV-1 and three broadly neutralizing antibodies (bNAbs) of the VRC01 class. The protocol has been adapted from successful studies of small molecules to address the challenges associated with modeling protein-protein interactions...
November 28, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27907170/complementation-of-an-aglb-mutant-of-methanococcus-maripaludis-with-heterologous-oligosaccharyltransferases
#4
Yan Ding, Helen A Vrionis, James Schneider, Alison Berezuk, Cezar M Khursigara, Ken F Jarrell
The oligosaccharyltransferase is the signature enzyme for N-linked glycosylation in all domains of life. In Archaea, this enzyme termed AglB, is responsible for transferring lipid carrier-linked glycans to select asparagine residues in a variety of target proteins including archaellins, S-layer proteins and pilins. This study investigated the ability of a variety of AglBs to compensate for the oligosaccharyltransferase activity in Methanococcus maripaludis deleted for aglB, using archaellin FlaB2 as the reporter protein since all archaellins in Mc...
2016: PloS One
https://www.readbyqxmd.com/read/27904760/serum-glycoprotein-derived-n-and-o-linked-glycans-as-cancer-biomarkers
#5
REVIEW
Ying Lan, Cui Hao, Xuan Zeng, Yanli He, Pengjiao Zeng, Zhihua Guo, Lijuan Zhang
Early detection of cancer is the key to improving survival. Since most clinically used serum cancer biomarkers are either glycoproteins or glycan structures that can be recognized by specific monoclonal antibodies, developing glycan structure-based biomarkers from human serum/plasma glycoproteins through mass spectrometry (MS) analysis are active research field during the past decades. Numerous studies have shown that changes in serum/plasma glycan structures occur during cancer initiation, progression, and treatment...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27903635/bacterial-polysaccharide-specificity-of-the-pattern-recognition-receptor-langerin-is-highly-species-dependent
#6
Jonas Hanske, Jessica Schulze, Jonas Aretz, Ryan McBride, Bernhard Loll, Henrik Schmidt, Yuriy Knirel, Wolfgang Rabsch, Markus C Wahl, James C Paulson, Christoph Rademacher
The recognition of pathogen surface polysaccharides by glycan-binding proteins is a cornerstone of innate host defense. Many members of the C-type lectin receptor family serve as pattern recognition receptors facilitating pathogen uptake, antigen processing, and immunomodulation. Despite the high evolutionary pressure in host-pathogen interactions, it is still widely assumed that genetic homology conveys similar specificities. Here, we investigate the ligand specificities of the human and murine forms of the myeloid C-type lectin receptor Langerin for simple and complex ligands augmented by structural insight on murine Langerin...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27902713/association-of-n-linked-glycoprotein-acetyls-and-colorectal-cancer-incidence-and-mortality
#7
Paulette D Chandler, Akintunde O Akinkuolie, Deirdre K Tobias, Patrick R Lawler, Chungying Li, M Vinayaga Moorthy, Lu Wang, Daniel A Duprez, David R Jacobs, Robert J Glynn, James Otvos, Margery A Connelly, Wendy S Post, Paul M Ridker, JoAnn E Manson, Julie E Buring, I-Min Lee, Samia Mora
BACKGROUND: Acute phase proteins highlight the dynamic interaction between inflammation and oncogenesis. GlycA, a novel nuclear magnetic resonance (NMR) inflammatory marker that identifies primarily circulating N-acetyl glycan groups attached to acute phase proteins, may be a future CRC risk biomarker. METHODS: We examined the association between GlycA and incident CRC and mortality in two prospective cohorts (N = 34,320); Discovery cohort: 27,495 participants from Women's Health Study (WHS); Replication cohort: 6,784 participants from Multi-Ethnic Study of Atherosclerosis (MESA)...
2016: PloS One
https://www.readbyqxmd.com/read/27902333/plant-produced-anti-dengue-virus-monoclonal-antibodies-exhibit-reduced-antibody-dependent-enhancement-of-infection-activity
#8
Matthew Dent, Jonathan Hurtado, Amber M Paul, Haiyan Sun, Huafang Lai, Ming Yang, Adrian Esqueda, Fengwei Bai, Herta Steinkellner, Qiang Chen
The monoclonal antibody (mAb) E60 has the potential to be a desirable therapeutic molecule since it efficiently neutralizes all four serotypes of dengue virus (DENV). However, mammalian cell-produced E60 exhibits antibody-dependent enhancement of infection (ADE) activity, rendering it inefficacious in vivo and subjects treated animals more susceptible to develop more severe diseases during secondary infection. In this study, we evaluated a plant-based expression system for the production of therapeutically suitable E60...
October 20, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27900805/effect-of-preorganized-charge-display-on-the-cell-penetrating-properties-of-cationic-peptides
#9
Yvonne A Nagel, Philipp S Raschle, Helma Wennemers
The effect of preorganized versus undefined charge display on the cellular uptake of cationic cell-penetrating peptides (CPPs) was investigated by comparing conformationally well-defined guanidinylated oligoprolines with flexible oligoarginines. Flow cytometry and confocal microscopy studies with different cancer cell lines (HeLa, MCF-7, and HT-29) showed that preorganization of cationic charges in lateral distances of ≈9 Å enhanced the cellular uptake of CPPs. Binding affinity measurements revealed tighter binding of analogues of cell-surface glycans to the guanidinylated octaproline with localized charges compared to flexible octaarginine, a finding that was further correlated to the cellular uptake by studies with CHO cells deficient in glycans on the outer plasma membrane...
November 30, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27900782/residue-centric-modeling-and-design-of-saccharide-and-glycoconjugate-structures
#10
Jason W Labonte, Jared Adolf-Bryfogle, William R Schief, Jeffrey J Gray
The RosettaCarbohydrate framework is a new tool for modeling a wide variety of saccharide and glycoconjugate structures. This report describes the development of the framework and highlights its applications. The framework integrates with established protocols within the Rosetta modeling and design suite, and it handles the vast complexity and variety of carbohydrate molecules, including branching and sugar modifications. To address challenges of sampling and scoring, RosettaCarbohydrate can sample glycosidic bonds, side-chain conformations, and ring forms, and it utilizes a glycan-specific term within its scoring function...
November 30, 2016: Journal of Computational Chemistry
https://www.readbyqxmd.com/read/27899244/editorial-overview-carbohydrate-protein-interactions-and-glycosylation-integrating-structural-biology-informatics-and-systems-modelling-to-understand-glycan-structure-and-glycan-protein-interactions
#11
EDITORIAL
Harry J Gilbert, Nagasuma Chandra
No abstract text is available yet for this article.
November 26, 2016: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/27899180/syncytiotrophoblast-extracellular-vesicles-circulating-biopsies-reflecting-placental-health
#12
Dionne Tannetta, Gavin Collett, Manu Vatish, Chris Redman, Ian Sargent
The ability to directly monitor the status of the placenta throughout pregnancy would be a major advance in both general and personalized obstetric care, allowing treatments to be tailored to the dynamic changes that can occur in gestation. Syncytiotrophoblast extracellular vesicles (STBEV) are membrane bound vesicles, released from the surface of the placenta directly into the maternal circulation, in the form of exosomes, microvesicles and apoptotic bodies. They carry many syncytiotrophoblast derived factors such as proteins, lipids, glycans and nucleic acids, which together could dynamically signal to the mother the status of the placenta...
November 16, 2016: Placenta
https://www.readbyqxmd.com/read/27898729/rna-contaminates-glycosaminoglycans-extracted-from-cells-and-tissues
#13
Jasper J van Gemst, Markus A Loeven, Mark J J de Graaf, Jo H M Berden, Ton J Rabelink, Cornelis H Smit, Johan van der Vlag
Glycosaminoglycans (GAGs) are linear negatively charged polysaccharides and important components of extracellular matrices and cell surface glycan layers such as the endothelial glycocalyx. The GAG family includes sulfated heparin, heparan sulfate (HS), dermatan sulfate (DS), chondroitin sulfate (CS), keratan sulfate, and non-sulfated hyaluronan. Because relative expression of GAGs is dependent on cell-type and niche, isolating GAGs from cell cultures and tissues may provide insight into cell- and tissue-specific GAG structure and functions...
2016: PloS One
https://www.readbyqxmd.com/read/27898009/effects-of-glycosylation-on-the-enzymatic-activity-and-mechanisms-of-proteases
#14
REVIEW
Peter Goettig
Posttranslational modifications are an important feature of most proteases in higher organisms, such as the conversion of inactive zymogens into active proteases. To date, little information is available on the role of glycosylation and functional implications for secreted proteases. Besides a stabilizing effect and protection against proteolysis, several proteases show a significant influence of glycosylation on the catalytic activity. Glycans can alter the substrate recognition, the specificity and binding affinity, as well as the turnover rates...
November 25, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27895507/fc-gamma-receptors-glycobiology-and-therapeutic-prospects
#15
REVIEW
Jerrard M Hayes, Mark R Wormald, Pauline M Rudd, Gavin P Davey
Therapeutic antibodies hold great promise for the treatment of cancer and autoimmune diseases, and developments in antibody-drug conjugates and bispecific antibodies continue to enhance treatment options for patients. Immunoglobulin (Ig) G antibodies are proteins with complex modifications, which have a significant impact on their function. The most important of these modifications is glycosylation, the addition of conserved glycans to the antibody Fc region, which is critical for its interaction with the immune system and induction of effector activities such as antibody-dependent cell cytotoxicity, complement activation and phagocytosis...
2016: Journal of Inflammation Research
https://www.readbyqxmd.com/read/27895315/identification-of-aberrantly-expressed-glycans-in-gastric-cancer-by-integrated-lectin-microarray-and-mass-spectrometric-analyses
#16
Xiang Li, Feng Guan, Dongliang Li, Zengqi Tan, Ganglong Yang, Yanli Wu, Zhaohui Huang
Cancer progression is usually associated with alterations of glycan expression patterns. Little is known regarding global glycomics in gastric cancer, the most common type of epithelial cancer. We integrated lectin microarray and mass spectrometry (MS) methods to profile glycan expression in three gastric cancer cell lines (SGC-7901, HGC-27, and MGC-803) and one normal gastric epithelial cell line (GES-1). Significantly altered glycans were confirmed by lectin staining and MALDI-TOF/TOF-MS. The three cancer cell lines showed increased levels of core-fucosylated N-glycans, GalNAcα-Ser/Thr (Tn antigen), and Sia2-6Galβ1-4GlcNAc N-glycans, but reduced levels of biantennary N-glycans, Galβ1-3GalNAcα-Ser/Thr (T antigen), and (GlcNAc)n N-glycans...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27894254/divergent-selection-induced-obesity-alters-the-composition-and-functional-pathways-of-chicken-gut-microbiota
#17
Jinmei Ding, Lele Zhao, Lifeng Wang, Wenjing Zhao, Zhengxiao Zhai, Li Leng, Yuxiang Wang, Chuan He, Yan Zhang, Heping Zhang, Hui Li, He Meng
BACKGROUND: The gastrointestinal tract is populated by a complex and vast microbial network, with a composition that reflects the relationships of the symbiosis, co-metabolism, and co-evolution of these microorganisms with their host. The mechanism that underlies such interactions between the genetics of the host and gut microbiota remains elusive. RESULTS: To understand how genetic variation of the host shapes the gut microbiota and interacts with it to affect the metabolic phenotype of the host, we compared the abundance of microbial taxa and their functional performance between two lines of chickens (fat and lean) that had undergone long-term divergent selection for abdominal fat pad weight, which resulted in a 4...
November 28, 2016: Genetics, Selection, Evolution: GSE
https://www.readbyqxmd.com/read/27893774/multivalent-interactions-of-human-primary-amine-oxidase-with-the-v-and-c22-domains-of-sialic-acid-binding-immunoglobulin-like-lectin-9-regulate-its-binding-and-amine-oxidase-activity
#18
Heli Elovaara, Vimal Parkash, Ruth Fair-Mäkelä, Outi M H Salo-Ahen, Gabriela Guédez, Eva Bligt-Lindén, Janne Grönholm, Sirpa Jalkanen, Tiina A Salminen
Sialic acid-binding immunoglobulin-like lectin-9 (Siglec-9) on leukocyte surface is a counter-receptor for endothelial cell surface adhesin, human primary amine oxidase (hAOC3), a target protein for anti-inflammatory agents. This interaction can be used to detect inflammation and cancer in vivo, since the labeled peptides derived from the second C2 domain (C22) of Siglec-9 specifically bind to the inflammation-inducible hAOC3. As limited knowledge on the interaction between Siglec-9 and hAOC3 has hampered both hAOC3-targeted drug design and in vivo imaging applications, we have now produced and purified the extracellular region of Siglec-9 (Siglec-9-EC) consisting of the V, C21 and C22 domains, modeled its 3D structure and characterized the hAOC3-Siglec-9 interactions using biophysical methods and activity/inhibition assays...
2016: PloS One
https://www.readbyqxmd.com/read/27891772/twoplex-12-13-c6-aniline-stable-isotope-and-linkage-specific-sialic-acid-labelling-2d-lc-ms-workflow-for-quantitative-n-glycomics
#19
Simone Albrecht, Stefan Mittermayr, Josh Smith, Silvia Millán Martín, Margaret Doherty, Jonathan Bones
Quantitative glycomics represents an actively expanding research field ranging from the discovery of disease associated glycan alterations to the quantitative characterization of N-glycans on therapeutic proteins. Commonly used analytical platforms for comparative relative quantitation of complex glycan samples include MALDI-ToF-MS or chromatographic glycan profiling with subsequent data alignment and statistical evaluation. Limitations of such approaches include run-to-run technical variation and the potential introduction of subjectivity during data processing...
November 28, 2016: Proteomics
https://www.readbyqxmd.com/read/27890857/structural-insights-into-a-family-39-glycoside-hydrolase-from-the-gut-symbiont-bacteroides-cellulosilyticus-wh2
#20
Ahmad Ali-Ahmad, Marie-Line Garron, Véronique Zamboni, Nicolas Lenfant, Didier Nurizzo, Bernard Henrissat, Jean-Guy Berrin, Yves Bourne, Florence Vincent
Bacteria from the human gut are equipped with an arsenal of carbohydrate-active enzymes that degrade dietary and host-derived glycans. In this study, we present the 2.5Å resolution crystal structure of a member (GH39wh2) from the human gut bacteria Bacteroides cellulosilyticus WH2 representative of a new subgroup within family GH39. Together with 6 other GHs, GH39wh2 belongs to a polysaccharide utilization locus (PUL) that could be involved in detecting, binding and hydrolysing a specific carbohydrate species from the intestinal tract...
November 24, 2016: Journal of Structural Biology
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