A5034207673- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- RNA and protein synthesis mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Protein Structure and Dynamics
- Genomics and Phylogenetic Studies
- Advanced NMR Techniques and Applications
- Enzyme Structure and Function
- Bacterial Genetics and Biotechnology
- Protein purification and stability
- Chemical Synthesis and Analysis
- Electron Spin Resonance Studies
- Bacteriophages and microbial interactions
- Transgenic Plants and Applications
- RNA Research and Splicing
- Microbial infections and disease research
- Galectins and Cancer Biology
- Insect Resistance and Genetics
- Toxin Mechanisms and Immunotoxins
- Cancer-related gene regulation
- Plant Parasitism and Resistance
- Bacterial Infections and Vaccines
- Molecular spectroscopy and chirality
- Enzyme Production and Characterization
- Insect-Plant Interactions and Control
University of Salzburg
2016-2025
Freie Universität Berlin
1997-2025
ETH Zurich
2010-2024
Instituto de Química Médica
2019
Consejo Superior de Investigaciones Científicas
2019
University of Zurich
2012
University of British Columbia
2004-2007
University College Dublin
2007
Canada's Michael Smith Genome Sciences Centre
2006
Leibniz-Forschungsinstitut für Molekulare Pharmakologie
1999-2005
Abstract Starch contains phosphate covalently bound to the C6-position (70 80% of total phosphate) and C3-position (20 30%) glucosyl residues amylopectin fraction. In plants, transient phosphorylation starch renders granule surface more accessible glucan hydrolyzing enzymes is required for proper degradation. Phosphate also confers desired properties starch-derived pastes industrial applications. Arabidopsis thaliana, removal by phosphatase Excess4 (SEX4) essential breakdown. We identified a...
δ-secretase, also known as asparagine endopeptidase (AEP) or legumain, is a lysosomal cysteine protease that cleaves both amyloid precursor protein (APP) and tau, mediating the amyloid-β tau pathology in Alzheimer's disease (AD). Here we report therapeutic effect of an orally bioactive brain permeable δ-secretase inhibitor mouse models AD. We performed high-throughput screen identified non-toxic selective inhibitor, termed compound 11, specifically blocks but not other related proteases....
N-Linked glycosylation is a frequent protein modification that occurs in all three domains of life. This process involves the transfer preassembled oligosaccharide from lipid donor to asparagine side chains polypeptides and catalyzed by membrane-bound oligosaccharyltransferase (OST). We characterized an alternative bacterial pathway wherein cytoplasmic N-glycosyltransferase uses nucleotide-activated monosaccharides as donors modify residues peptides proteins. N-Glycosyltransferase inverting...
The carbon storage regulator/regulator of secondary metabolism (Csr/Rsm) type small non-coding RNAs (sRNAs) is widespread throughout bacteria and acts by sequestering the global translation repressor protein CsrA/RsmE from ribosome binding site a subset mRNAs. Although we have previously described molecular basis high affinity RNA target bound to RsmE, it remains unknown how other lower targets are recognized same protein. Here, determined nuclear magnetic resonance solution structures five...
Significance Siglec-8 downregulates eosinophil- and mast cell-mediated inflammatory responses upon engagement by specific self-glycans. We used solution NMR spectroscopy to determine the structure of N-terminal lectin domain human in complex with its preferred glycan target 6′-sulfo sialyl Lewis x . Quantitative binding studies differently sulfated glycans structure-based mutants demonstrate that simultaneously recognizes a terminal N -acetylneuraminic acid (sialic acid) an underlying 6- O...
Discrimination between self and non-self is a prerequisite for any defence mechanism; in innate defence, this discrimination often mediated by lectins recognizing carbohydrate structures so relies on an arsenal of host with different specificities towards target organism structures. Recently, cytoplasmic isolated from fungal fruiting bodies have been shown to play role the multicellular fungi against predators parasites. Here, we present novel body lectin, CCL2, ink cap mushroom Coprinopsis...
Although animal lectins usually show a high degree of specificity for glycan structures, their single-site binding affinities are typically weak, drawback which is often compensated in biological systems by an oligovalent presentation carbohydrate epitopes. For the design monovalent glycomimetics, structural information regarding solution and bound conformation lead represents valuable starting point. In this paper, we focus on trisaccharide Lex (Gal[Fucα(1–3)]β(1–4)GlcNAc). Mainly because...
Although there is great interest in three-dimensional structures of glycoproteins and complex oligosaccharides, their structural determination have been hampered by inhomogeneous incomplete glycosylation, poor expression, low tendency to crystallize, severe chemical shift overlap. Using segmental labeling the glycan protein component vitro we developed a novel method NMR that overcomes some these problems. Highly homogeneously glycosylated proteins milligram amounts can be obtained. This...
The three-dimensional structure determination of RNAs by NMR spectroscopy relies on chemical shift assignment, which still constitutes a bottleneck. In order to develop more efficient assignment strategies, we analysed relationships between sequence and (1)H (13)C shifts. Statistics resonances from regularly Watson-Crick base-paired RNA revealed highly characteristic clusters. We developed two approaches using these statistics for double-stranded (dsRNA): manual approach that yields starting...
N-Linked protein glycosylation is a very common post-translational modification that can be found in all kingdoms of life. The classical, highly conserved pathway entails the assembly lipid-linked oligosaccharide and its transfer to an asparagine residue sequon NX(S/T) secreted by integral membrane oligosaccharyltransferase. A few species class γ-proteobacteria encode cytoplasmic N-glycosylation system mediated soluble N-glycosyltransferase (NGT). This enzyme uses nucleotide-activated sugars...
Abstract Posttranslational modifications (PTMs) are an integral part of the majority proteins. The characterization structure and function PTMs can be very challenging especially for glycans. Existing methods to analyze require complicated sample preparations suffer from missing certain modifications, inability identify linkage types thus chemical structure. We present a direct, robust, simple NMR spectroscopy method detection identification in No isotope labeling is required, nor does...
Bacterial capsules have critical roles in host-pathogen interactions. They provide a protective envelope against host recognition, leading to immune evasion and bacterial survival. Here we define the capsule biosynthesis pathway of Haemophilus influenzae serotype b (Hib), Gram-negative bacterium that causes severe infections infants children. Reconstitution this enabled fermentation-free production Hib vaccine antigens starting from widely available precursors detailed characterization...
Abstract Capsules are long-chain carbohydrate polymers that envelop the surfaces of many bacteria, protecting them from host immune responses. Capsule biosynthesis enzymes potential drug targets and valuable biotechnological tools for generating vaccine antigens. Despite their importance, it remains unknown how structurally variable capsule Gram-negative pathogens linked to conserved glycolipid anchoring these virulence factors bacterial membrane. Using Actinobacillus pleuropneumoniae as an...
Human sialic-acid-binding immunoglobulin-like lectin-9 (Siglec-9) is a glycoimmune checkpoint receptor expressed on several immune cells. Binding of Siglec-9 to sialic acid containing glycans (sialoglycans) well documented modulate its functions as an inhibitory receptor. Here, we first assigned the amino backbone V-set domain (Siglec-9
Abstract The increasing understanding of the essential role carbohydrates in development, and a wide range diseases fuels rapidly growing interest basic principles governing carbohydrate‐protein interactions. A still heavily debated issue regarding recognition process is degree flexibility or rigidity oligosaccharides. Combining NMR structure determination based on extensive experimental data with DFT database searches, we have identified set trisaccharide motifs similar conformation that...
ABSTRACT Group 2 capsule polymers represent crucial virulence factors of Gram-negative pathogenic bacteria. They are synthesized by enzymes called polymerases. In this report, we describe a new family polymerases that combine glycosyltransferase and hexose- polyol-phosphate transferase activity to generate complex poly(oligosaccharide phosphate) poly(glycosylpolyol polymers, the latter which display similarity wall teichoic acid (WTA), cell component Gram-positive Using modeling...