A5069789352- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Galectins and Cancer Biology
- RNA and protein synthesis mechanisms
- Viral Infections and Immunology Research
- Extracellular vesicles in disease
- Cytomegalovirus and herpesvirus research
- Parasitic Infections and Diagnostics
- Virus-based gene therapy research
- Biochemical and Molecular Research
- Viral gastroenteritis research and epidemiology
- SARS-CoV-2 and COVID-19 Research
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Pulmonary Hypertension Research and Treatments
- Silicone and Siloxane Chemistry
- Viral Infectious Diseases and Gene Expression in Insects
- CAR-T cell therapy research
- Inhalation and Respiratory Drug Delivery
- Lysosomal Storage Disorders Research
- Radiopharmaceutical Chemistry and Applications
- Inorganic Fluorides and Related Compounds
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Cancer-related Molecular Pathways
University of Groningen
2023-2025
University Medical Center Groningen
2025
Umeå University
2020-2024
University of Dundee
2013-2023
MRC Protein Phosphorylation and Ubiquitylation Unit
2013-2023
Medical Research Council
2015-2023
Abstract Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, with a significant impact on low‐ and middle‐income countries, making it critical challenge for global health equity sustainable development goals. Extracellular vesicles (EVs) are emerging as promising treatment COPD, but conventional storage at −80 °C limits their accessibility. This study explores alternative methods to enhance EV stability accessibility, particularly in low‐resource...
Significance The adenovirus capsid protein is built by three main capsomers: hexon, fiber, and penton base. Entry mediated fiber proteins anchoring the virus to host cell receptors followed base engaging coreceptors, resulting in entry. Here, we demonstrate that human species D types, which constitute two-thirds of all adenoviruses, enter cells through a direct interaction between hexon CD46. This study provides insights into entry mechanisms used adenoviruses. As these viruses are also as...
Human adenovirus (HAdV) types F40 and F41 are a prominent cause of diarrhea diarrhea-associated mortality in young children worldwide. These enteric HAdVs differ notably tissue tropism pathogenicity from respiratory ocular adenoviruses, but the structural basis for this divergence has been unknown. Here, we present first structure an HAdV-HAdV-F41-determined by cryo-electron microscopy to resolution 3.8 Å. The reveals extensive alterations virion exterior as compared nonenteric HAdVs,...
Inhibitors of OGT (O-GlcNAc transferase) are valuable tools to study the cell biology protein O-GlcNAcylation. We report bisubstrate-linked inhibitors (goblins) in which acceptor serine peptide VTPVSTA is covalently linked UDP, eliminating GlcNAc pyranoside ring. Goblin1 co-crystallizes with OGT, revealing an ordered C₃ linker and retained substrate-binding modes, binds enzyme micromolar affinity, inhibiting glycosyltransfer on substrates.
O-linked N -acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. Although a single enzyme, O-GlcNAc transferase (OGT), generates the entire cytosolic proteome, it not understood how recognizes its protein substrates, targeting only fraction serines/threonines metazoan proteome for glycosylation. We describe trapped complex human OGT with C-terminal domain TAB1, key innate immunity-signalling...
O-GlcNAc transferase (OGT) is an essential glycosyltransferase that installs the post-translational modification on nucleocytoplasmic proteome. We report development of S-linked UDP–peptide conjugates as potent bisubstrate OGT inhibitors. These compounds were assembled in a modular fashion by photoinitiated thiol–ene conjugation allyl-UDP and optimal acceptor peptides which serine was replaced with cysteine. The conjugate VTPVC(S-propyl-UDP)TA (Ki = 1.3 μM) inhibits activity HeLa cell...
Background: Alzheimer’s Disease (AD) represents a significant public health challenge with rising global burden. Emerging evidence suggests potential link between herpes zoster (HZ) and an increased risk of AD. These findings indicate that HZ may contribute to neuroinflammation other pathophysiological processes associated AD, pointing out the role virus infection in initiation and/or progression AD pathology. Objective: This systematic review evaluates relationships highlighting...
O-GlcNAcylation is one of the most abundant metazoan nuclear-cytoplasmic post-translational modifications. Proteins modified by O-GlcNAc play key cellular roles in signaling, transcription, metabolism, and cell division. Mechanistic studies on protein are hampered lack methods that can simultaneously quantify O-GlcNAcylation, determine its stoichiometry, monitor kinetics. Here, we demonstrate high-resolution native mass spectrometry be employed to small shifts induced modification two known...
The attachment of the sugar N-acetyl-D-glucosamine (GlcNAc) to specific serine and threonine residues on proteins is referred as protein O-GlcNAcylation. O-GlcNAc transferase (OGT) enzyme responsible for carrying out modification, while O-GlcNAcase (OGA) reverses it. Protein O-GlcNAcylation has been implicated in a wide range cellular processes including transcription, proteostasis, stress response. Dysregulation linked diabetes, cancer, neurodegenerative cardiovascular disease. OGA proposed...
Abstract A series of glycomimetics UDP‐GlcNAc, in which the β‐phosphate has been replaced by either an alkyl chain or a triazolyl ring and sugar moiety pyrrolidine ring, synthesized application different click‐chemistry procedures. Their affinities for human O‐GlcNAc transferase (hOGT) have evaluated studied both spectroscopically computationally. The binding epitopes best ligands determined solution means saturation transfer difference (STD) NMR spectroscopy. Experimental, spectroscopic,...
Chronic obstructive pulmonary disease (COPD) is a progressive lung for which there no cure. Accumulating research results suggest role extracellular vesicles (EVs) in the pathogenesis of COPD. This study aimed to uncover involvement EVs and their molecular cargo progression COPD by identification EV-associated protein microRNA (miRNA) profiles. We isolated from bronchial alveolar lavage fluid (BALF) 18 patients with 11 healthy controls using size-exclusion chromatography. EV isolates were...
Nonstructural protein 1 (Nsp1) of SARS-CoV-2 inhibits host cell translation through an interaction between its C-terminal domain and the 40S ribosome. The N-terminal (NTD) Nsp1 is a target recurring deletions, some which are associated with altered COVID-19 disease progression. Here, we characterize efficiency translational inhibition by clinically observed deletion variants. We show that frequent residues 79-89 severely reduces ability to inhibit while not abrogating binding 40S. Notably,...
Abstract The protozoan parasite Giardia intestinalis is one of only a few organisms lacking de novo synthesis DNA building blocks (deoxyribonucleotides). Instead, the relies exclusively on salvaging deoxyadenosine and other deoxyribonucleosides from its host environment. Here, we report that G. has deoxyribonucleoside kinase with 1000-fold higher catalytic efficiency (kcat/KM) for than corresponding mammalian kinases can thereby provide sufficient triphosphate levels despite lack synthesis....
Abstract Human adenovirus (HAdV) types F40 and F41 are a prominent cause of diarrhea diarrhea-associated mortality in young children worldwide. These enteric HAdVs differ strikingly tissue tropism pathogenicity from respiratory ocular adenoviruses, but the structural basis for this divergence has been unknown. Here we present first structure an HAdV - HAdV-F41 determined by cryo-EM to resolution 3.8Å. The reveals extensive alterations virion exterior as compared non-enteric HAdVs, including...