A5064572925- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Carbohydrate Chemistry and Synthesis
- Streptococcal Infections and Treatments
- Neonatal and Maternal Infections
- Infant Nutrition and Health
- Antimicrobial Resistance in Staphylococcus
- HER2/EGFR in Cancer Research
- Galectins and Cancer Biology
- Protein purification and stability
- Platelet Disorders and Treatments
- Seaweed-derived Bioactive Compounds
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Heparin-Induced Thrombocytopenia and Thrombosis
- Biochemical and Structural Characterization
- Mass Spectrometry Techniques and Applications
- Advanced Proteomics Techniques and Applications
- Blood groups and transfusion
- Immunodeficiency and Autoimmune Disorders
- Neonatal Health and Biochemistry
- Transgenic Plants and Applications
- Legionella and Acanthamoeba research
- Autoimmune Bullous Skin Diseases
- Microbial Metabolites in Food Biotechnology
- Chemical Synthesis and Analysis
Genovis (Sweden)
2013-2023
Lund University
2011-2021
Many bacteria have evolved ways to interact with glycosylation functions of the immune system their hosts. Streptococcus pyogenes [GAS (group A Streptococcus)] secretes enzyme EndoS that cleaves glycans on human IgG and impairs effector antibody. The ndoS gene, encoding EndoS, has, until now, been thought be conserved throughout serotypes. However, in present study, we identify EndoS2, an endoglycosidase serotype M49 GAS strains. We characterized EndoS2 corresponding ndoS2 gene using...
Abstract Akkermansia muciniphila is a mucin-degrading bacterium commonly found in the human gut that promotes beneficial effect on health, likely based regulation of mucus thickness and barrier integrity, but also modulation immune system. In this work, we focus OgpA from A. , an O -glycopeptidase exclusively hydrolyzes peptide bond N -terminal to serine or threonine residues substituted with -glycan. We determine high-resolution X-ray crystal structures unliganded form OgpA, complex...
Neutrophils are essential for host defense at the oral mucosa and neutropenia or functional neutrophil defects lead to disordered homeostasis. We found that neutrophils from harvested morning saliva had released extracellular traps (undergone NETosis) in vivo. The NETosis was mediated through intracellular signals elicited by binding of sialyl Lewis(X) present on salival mucins l-selectin neutrophils. This led rapid loss nuclear membrane release granule proteins with subsequent trap (NET)...
Glycosylation plays a critical role in the biosynthetic-secretory pathway endoplasmic reticulum (ER) and Golgi apparatus. Over 50% of mammalian cellular proteins are typically glycosylated; this modification is involved wide range biological functions such as barrier formation against intestinal microbes serves signaling molecules for selectins galectins innate immune system. N-linked glycosylation analysis has been greatly facilitated owing to specific enzymes available their release....
Enzymes that affect glycoproteins of the human immune system, and thereby modulate defense responses, are abundant among bacterial pathogens. Two endoglycosidases from pathogen Streptococcus pyogenes, EndoS EndoS2, have recently been shown to hydrolyze N-linked glycans immunoglobulin G. However, detailed characterization comparison hydrolyzing activities not performed. In present study, we set out characterize enzymes by comparing EndoS2 on a selection therapeutic monoclonal antibodies...
Abstract Red blood cell antigens play critical roles in transfusion since donor incompatibilities can be lethal. Recipients with the rare total deficiency H antigen, O h Bombay phenotype, only transfused group to avoid serious reactions. We discover FucOB from mucin-degrading bacteria Akkermansia muciniphila as an α-1,2-fucosidase able hydrolyze Type I, II, III and V obtain afucosylated phenotype vitro. X-ray crystal structures of show a three-domain architecture, including GH95 glycoside...
Abstract Background The secreted enzyme EndoS, an endoglycosidase from Streptococcus pyogenes , hydrolyzes the N -linked glycan of constant region immunoglobulin G (IgG) heavy chain and renders antibody unable to interact with Fc receptors elicit effector functions. In this study we couple targeted allelic replacement mutagenesis heterologous expression elucidate contribution EndoS group A (GAS) phagocyte resistance pathogenicity in vitro vivo . Results Knocking out gene GAS M1T1 background...
Antibody-drug conjugates (ADCs) are biotherapeutics consisting of a tumor-targeting monoclonal antibody (mAb) linked covalently to cytotoxic drug. Early generation ADCs were predominantly obtained through non-selective conjugation methods based on lysine and cysteine residues, resulting in heterogeneous populations with varying drug-to-antibody ratios (DAR). Site-specific is one the current challenges ADC development, allowing for controlled production homogeneous ADCs. We report here...
Glycosidases are widespread among bacteria. The opportunistic human pathogen Enterococcus faecalis encodes several putative glycosidases but little is known about their functions. identified endo-β-N-acetylglucosaminidase EndoE has activity on the N-linked glycans of immunoglobulin G (IgG). In this report we glycoprotein lactoferrin (hLF) as a new substrate for EndoE. Hydrolysis N-glycans from hLF was investigated using lectin blot, UHPLC and mass spectrometry, showing that releases major...
O-Glycoprotein analysis has been historically challenging due, in part, to a dearth of available enzymes active the release O-glycans. Moreover, chemical releasing methods, such as β-elimination/Michael addition, are not specific O-glycan and can also eliminate phosphoryl substitutions. Both these events leave behind deaminated serine threonine thus lead ambiguous structural conclusions. Recently, O-protease OpeRATOR, derived from intestinal bacteria expressed Escherichia coli, become...
Conventional antibody–drug conjugate (ADC) manufacturing methods are based on the nonselective bioconjugation of cytotoxic drugs to lysine and cysteine residues. This results in highly heterogeneous mixtures different drug–antibody ratios (DAR) that can significantly affect safety efficacy ADC product. Recently, an innovative procedure named GlyCLICK was suggested, consisting a two-step enzymatic transform Fc-glycans present IgG mAbs into two site-specific anchor points for conjugation any...
Aim: The aim of this study was to identify and characterize EndoS-like enzymes in Streptococcus dysgalactiae subspecies (SDSD). Materials & methods: PCR, DNA sequencing, recombinant protein expression, lectin blot, ultra high performance liquid chromatography analysis a chitinase assay were used ndoS-like genes EndoSd. Results: EndoSd found four SDSD strains. hydrolyzes the chitobiose core glycan on IgG. amino acid sequence is 70% identical EndoS S. pyogenes, but it has unique C-terminal...