A5062910532- Enzyme Structure and Function
- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Influenza Virus Research Studies
- Enzyme Production and Characterization
- Protein Structure and Dynamics
- Vibrio bacteria research studies
- Virology and Viral Diseases
- Amino Acid Enzymes and Metabolism
- Genomics and Phylogenetic Studies
- Monoclonal and Polyclonal Antibodies Research
- Pneumonia and Respiratory Infections
- Respiratory viral infections research
- Biochemical and Molecular Research
- Bacteriophages and microbial interactions
- Bacterial Infections and Vaccines
- Trypanosoma species research and implications
- HIV Research and Treatment
- RNA and protein synthesis mechanisms
- DNA and Nucleic Acid Chemistry
- Machine Learning in Bioinformatics
- Probiotics and Fermented Foods
- Bacterial Genetics and Biotechnology
- Escherichia coli research studies
- Peptidase Inhibition and Analysis
University of St Andrews
2010-2021
Medizinische Hochschule Hannover
2010
Johns Hopkins University
2010
Hohenstein Institute
2010
Johns Hopkins Medicine
2010
Western Infirmary
2007
Simon Fraser University
2005
BioCryst Pharmaceuticals (United States)
2004
Shriners Hospitals for Children - Cincinnati
2003
University of Bath
1992-2002
The crystal structure of the closed form citrate synthase, with and CoA bound, from hyperthermophilic Archaeon Pyrococcus furiosus has been determined to 1.9 Å. This allowed direct structural comparisons between same enzyme organisms growing optimally at 37 °C (pig), 55 (Thermoplasma acidophilum) now 100 (Pyrococcus furiosus). three enzymes are homodimers share a similar overall fold, dimer interface comprising primarily an eight α-helical sandwich four antiparallel pairs helices. active...
Sialidases (EC 3.2.1.18 or neuraminidases) remove sialic acid from sialoglycoconjugates, are widely distributed in nature, and have been implicated the pathogenesis of many diseases. The three-dimensional structure influenza virus sialidase is known, we now report a bacterial sialidase, Salmonella typhimurium LT2, at 2.0-A resolution its complex with inhibitor 2-deoxy-2,3-dehydro-N-acetylneuraminic 2.2-A resolution. viral enzyme tetramer; enzyme, monomer. Although monomers similar size...
ABSTRACT Neuraminidase inhibitors (NAIs) are antivirals designed to target conserved residues at the neuraminidase (NA) enzyme active site in influenza A and B viruses. The that interact with NAIs under selective pressure, but only a few have been linked resistance. In A/Wuhan/359/95 (H3N2) recombinant virus background, we characterized seven charged, NA (R118, R371, E227, R152, R224, E276, D151) directly not reported confer resistance NAIs. These were replaced amino acids possess side...
Paramyxoviruses are the leading cause of respiratory disease in children. Several paramyxoviruses possess a surface glycoprotein, hemagglutinin-neuraminidase (HN), that is involved attachment to sialic acid receptors, promotion fusion, and removal from infected cells progeny virions. Previously we showed Newcastle virus (NDV) HN contained pliable recognition site could take two states, binding state catalytic state. Here present evidence for second at dimer interface model its involvement...
Abstract The gastrointestinal mucus layer is colonized by a dense community of microbes catabolizing dietary and host carbohydrates during their expansion in the gut. Alterations mucosal carbohydrate availability impact on composition microbial species. Ruminococcus gnavus commensal anaerobe present tract >90% humans overrepresented inflammatory bowel diseases (IBD). Using combination genomics, enzymology crystallography, we show that mucin-degrader R. ATCC 29149 strain produces an...
Vibrio cholerae neuraminidase (VCNA) plays a significant role in the pathogenesis of cholera by removing sialic acid from higher order gangliosides to unmask GM1, receptor for toxin. We previously showed that structure VCNA is composed central beta-propeller catalytic domain flanked two lectin-like domains; however nature carbohydrates recognized these lectin domains has remained unknown. present here structures enzyme complex with substrates, alpha-2,3-sialyllactose and...
Paramyxovirus infects cells by initially attaching to a sialic acid-containing cellular receptor and subsequently fusing with the plasma membrane of cells. Hemagglutinin-neuraminidase (HN) protein, which is responsible for virus attachment, interacts fusion protein in type-specific manner induce efficient fusion. To elucidate mechanism HN-promoted fusion, we characterized series Newcastle disease HN proteins whose surface residues were mutated. Fusion promotion activity was substantially...
ABSTRACT We recently reported the first crystal structure of a paramyxovirus hemagglutinin-neuraminidase (HN) from Newcastle disease virus. This multifunctional protein is responsible for binding to cellular sialyl-glycoconjugate receptors, promotion fusion through interaction with second viral surface (F) glycoprotein, and processing progeny virions by removal sialic acid newly synthesized coat proteins. Our structural studies suggest that HN possesses single recognition site can be...
The Scottish Structural Proteomics Facility was funded to develop a laboratory scale approach high throughput structure determination. effort successful in that over 40 structures were determined. These and the methods harnessed obtain them are reported here. This report reflects on value of automation but also continued requirement for degree scientific technical expertise. efficiency process poses challenges current paradigm structural analysis publication. In 5 year period we published...
The ferric uptake regulator (Fur) is a metal-dependent DNA-binding protein that acts as both repressor and an activator of numerous genes involved in maintaining iron homeostasis bacteria. It has also been demonstrated Vibrio cholerae Fur plays additional role pathogenesis, opening up the potential drug target for cholera. Here we present crystal structure V. reveals very different orientation domains compared with observed Pseudomonas aeruginosa Fur. Each monomer dimeric contains two metal...
Clostridium perfringens is a Gram-positive bacterium responsible for bacteremia, gas gangrene, and occasionally food poisoning. Its genome encodes three sialidases, nanH, nanI, nanJ, that are involved in the removal of sialic acids from variety glycoconjugates play role bacterial nutrition pathogenesis. Recent studies on trypanosomal (trans-) sialidases have suggested catalysis all may proceed via covalent intermediate similar to other retaining glycosidases. Here we provide further evidence...
Streptococcus penumoniae is a major human pathogen responsible for respiratory tract infections, septicemia, and meningitis continues to produce numerous cases of disease with relatively high mortalities. S. pneumoniae encodes up three sialidases, NanA, NanB, NanC, that have been implicated in pathogenesis are potential drug targets. NanA has shown be promiscuous sialidase, hydrolyzing the removal Neu5Ac from variety glycoconjugates retention configuration at anomeric center, as we confirm...
ABSTRACT The E2 envelope glycoprotein of hepatitis C virus (HCV) binds to the host entry factor CD81 and is principal target for neutralizing antibodies (NAbs). Most NAbs recognize hypervariable region 1 on E2, which undergoes frequent mutation, thereby allowing evade neutralization. Consequently, there great interest in that conserved epitopes. One such NAb AP33, a mouse monoclonal antibody recognizes conserved, linear epitope potently neutralizes broad range HCV genotypes. In this study,...
When collecting X-ray diffraction data from a crystal, we measure the intensities of diffracted waves scattered series planes that can imagine slicing through crystal in all directions. From these derive amplitudes waves, but experiment lose phase information; is, how offset when add them together to reconstruct an image our molecule. This is generally known as `phase problem'. We only phases some knowledge molecular structure. In small-molecule crystallography, basic assumptions about...
Abstract Ruminococcus gnavus is a human gut symbiont wherein the ability to degrade mucins mediated by an intramolecular trans -sialidase ( Rg NanH). NanH comprises GH33 catalytic domain and sialic acid-binding carbohydrate-binding module (CBM40). Here we used glycan arrays, STD NMR, X-ray crystallography, mutagenesis binding assays determine structure function of NanH_CBM40 CBM40). CBM40 displays canonical β-sandwich fold broad specificity towards sialoglycans with millimolar affinity α2,3-...