A5073165481- Enzyme Production and Characterization
- Carbohydrate Chemistry and Synthesis
- Glycosylation and Glycoproteins Research
- Microbial Metabolites in Food Biotechnology
- Biofuel production and bioconversion
- Lysosomal Storage Disorders Research
- Enzyme Structure and Function
- Enzyme Catalysis and Immobilization
- Biochemical and Molecular Research
- Microbial Metabolic Engineering and Bioproduction
- Trypanosoma species research and implications
- Berberine and alkaloids research
- Bacterial Genetics and Biotechnology
- Galectins and Cancer Biology
- Probiotics and Fermented Foods
- Polysaccharides and Plant Cell Walls
- Plant Gene Expression Analysis
- Plant biochemistry and biosynthesis
- Diet, Metabolism, and Disease
- Bacteriophages and microbial interactions
- Synthesis and Catalytic Reactions
- Studies on Chitinases and Chitosanases
- Chemical Synthesis and Analysis
- RNA and protein synthesis mechanisms
- Microbial Natural Products and Biosynthesis
University of York
2014-2025
New York Structural Biology Center
2007-2017
The glucosylation of pollutant and pesticide metabolites in plants controls their bioactivity the formation subsequent chemical residues. model plant Arabidopsis thaliana contains >100 glycosyltransferases (GTs) dedicated to small-molecule conjugation and, whereas 44 these enzymes catalyze O-glucosylation chlorinated phenols, only one, UGT72B1, shows appreciable N-glucosylating activity toward chloroanilines. UGT72B1 is a bifunctional O-glucosyltransferase (OGT) N-glucosyltransferase (NGT)....
Alternatives to petroleum-based chemicals are highly sought-after for ongoing efforts reduce the damaging effects of human activity on environment. Copper radical oxidases from Auxiliary Activity Family 5/Subfamily 2 (AA5_2) attractive biocatalysts because they oxidize primary alcohols in a chemoselective manner without complex organic cofactors. However, despite numerous studies canonical galactose (GalOx, EC 1.1.3.9) and engineered variants, recent discovery Colletotrichum graminicola...
During infection, the human opportunistic pathogen Pseudomonas aeruginosa forms protective biofilms, whose matrix consists of proteins, nucleic acids, and polysaccharides such as alginate, Psl, Pel. a polymeric pentasaccharide composed mannose, rhamnose, glucose, is produced during early stages biofilm formation, serving barrier against antibiotics immune system. The Psl biosynthesis gene cluster, besides encoding various glycosyltransferases, also includes an endoglycosidase, PslG. Here, we...
The essential biological roles played by glycosidases, coupled to the diverse therapeutic benefits of pharmacologically targeting these enzymes, provide considerable motivation for development new inhibitor classes. Cyclophellitol epoxides and aziridines are recently established covalent glycosidase inactivators. Inspired application cyclic sulfates as electrophilic equivalents in organic synthesis, we sought test whether cyclophellitol cyclosulfates would similarly act irreversible...
The industrial conversion of cellulosic plant biomass into useful products such as biofuels is a major societal goal. These technologies harness diverse degrading enzymes, classical exo- and endo-acting cellulases and, increasingly, cellulose-active lytic polysaccharide monooxygenases, to deconstruct the recalcitrant β-D-linked polysaccharide. A drawback with this process that exo-acting cellobiohydrolases suffer from severe inhibition their cellobiose product. β-D-Glucosidases are therefore...
The enzymatic degradation of plant polysaccharides is emerging as one the key environmental goals early 21st century, impacting on many processes in textile and detergent industries well biomass conversion to biofuels. One known problems with use nonstarch (nonfood)-based substrates such cell wall that cellulose fibers are embedded a network diverse polysaccharides, including xyloglucan, renders access difficult. There therefore increasing interest "accessory enzymes," xyloglucanases, may...
Deoxygenated cyclophellitol aziridines enable activity-based inter-class labeling of glycosidases including LC-MS/MS identification.
The enzyme-catalysed degradation of starch is central to many industrial processes, including sugar manufacture and first-generation biofuels. Classical biotechnological platforms involve steam explosion followed by the action endo-acting glycoside hydrolases termed α-amylases then exo-acting α-glucosidases (glucoamylases) yield glucose, which subsequently processed. A key enzymatic player in this pipeline `Termamyl' class bacterial designed/evolved variants thereof. Here, three-dimensional...
Xyloglucan (XyG) is a ubiquitous and fundamental polysaccharide of plant cell walls. Due to its structural complexity, XyG requires combination backbone-cleaving sidechain-debranching enzymes for complete deconstruction into component monosaccharides. The soil saprophyte Cellvibrio japonicus has emerged as genetically tractable model system study biomass saccharification, in part due innate capacity utilize wide range polysaccharides growth. Whereas the downstream debranching xyloglucan...
The conformational analysis of glycosidases affords a route to their specific inhibition through transition-state mimicry. Inspired by the rapid reaction rates cyclophellitol and aziridine—both covalent retaining β-glucosidase inhibitors—we postulated that corresponding carba "cyclopropyl" analogue would be potent inhibitor for those enzymes reacting 4H3 conformation. Ab initio metadynamics simulations free energy landscape cyclopropyl inhibitors show strong bias conformation,...
β-N-acetylhexosaminidases (HEX) are glycosidases that catalyze the glycosidic linkage hydrolysis of gluco- and galacto-configured N-acetyl-β-d-hexosaminides. These enzymes important in human physiology candidates for biocatalytic production carbohydrates glycomimetics. In this study, three-dimensional structure wild-type catalytically impaired E302Q HEX variant from soil bacterium Streptomyces coelicolor A3(2) (ScHEX) were solved ligand-free forms presence 6-acetamido-6-deoxy-castanospermine...
Bacteria and yeasts grow on biomass polysaccharides by expressing excreting a complex array of glycoside hydrolase (GH) enzymes. Identification annotation such GH pools, which are valuable commodities for sustainable energy chemistries, conventional means (genomics, proteomics) complicated, as primary sequence or secondary structure alignment with known active enzymes is not always predictive new ones. Here we report "low-tech", easy-to-use, sensitive multiplexing activity-based...
The opium poppy, Papaver somniferum, has been a source of medicinal alkaloids since the earliest civilizations, ca. 3400 B.C. benzylisoquinoline alkaloid noscapine is produced commercially in P. somniferum for use as cough suppressant, and it also potential an anticancer compound. first committed step recently elucidated biosynthetic pathway involves conversion scoulerine to tetrahydrocolumbamine by 9-O-methylation, catalyzed O-methyltransferase 1 (PSMT1). We demonstrate, through protein...
Gluco-azoles competitively inhibit glucosidases by transition-state mimicry and their ability to interact with catalytic acid residues in glucosidase active sites. We noted that no azole-type inhibitors described, date, possess a protic nitrogen characteristic for 1H-imidazoles. Here, we present gluco-1H-imidazole, gluco-azole bearing 1H-imidazole fused glucopyranose-configured cyclitol core, three close analogues as new inhibitors. All compounds human retaining β-glucosidase, GBA1, the most...
The Michaelis complex of the β-mannosidase Man2A shows distortion to a 1S5 conformation adding growing body evidence supporting catalysis through boat conformation.
The recently discovered futalosine pathway is a promising target for the development of new antibiotics. enzymes involved in this are crucial biosynthesis essential prokaryotic respiratory compound menaquinone, and as limited to few bacterial species such gastric pathogen Helicobacter pylori it potential specific In report, crystal structure an H. methylthioadenosine nucleosidase (MTAN; enzyme with broad specificity activity towards 6-amino-6-deoxyfutalosine), which second step menaquinone...
Xyloglucan (XyG) is a complex polysaccharide that ubiquitous and often abundant in the cell walls of terrestrial plants.
Acid β-galactosidase (GLB1) and galactocerebrosidase (GALC) are retaining exo-β-galactosidases involved in lysosomal glycoconjugate metabolism.