Crystal structure of New Delhi metallo-β-lactamase reveals molecular basis for antibiotic resistance. University of British Columbia | Publication | 2011-09-01 | |
Thermal Proteome Profiling Reveals the O-GlcNAc-Dependent Meltome.Other University of British Columbia, Simon Fraser University | Publication | 2022-03-01 | |
Both Chemical and Non-Chemical Steps Limit the Catalytic Efficiency of Family 4 Glycoside Hydrolases Simon Fraser University | Publication | 2018-04-01 | Natalia Sannikova, Chloe A N Gerak, Fahimeh Sadat Shidmoossavee, Dustin King, Saeideh Shamsi Kazem Abadi, Andrew Ross Lewis, Andrew Bennet |
Structural and Functional Insight into Human O-GlcNAcase Simon Fraser University | Publication | 2017-01-01 | Roth Christian, Sherry Chan, Wendy Offen, Glyn Hemsworth, Lianne Willems, Dustin King, Vimal Varghese, Robert Britton, David Vocadlo, Gideon Davies(CA) |
Fluorescence-Quenched Substrates for Quantitative Live Cell Imaging of Glucocerebrosidase ActivityRG-1 Simon Fraser University | Publication | 2018-01-01 | |
Direct one-step fluorescent labeling of O-GlcNAc modified proteins in live cells using metabolic intermediatesCD-1 Simon Fraser University | Publication | 2018-10-01 | HongYee Tan, Razieh Eskandari, David Shen, Yanping Zhu, Ta-Wei Liu, Lianne I Willems, Matt Alteen, Zarina Madden, David Vocadlo |
O-glycosylation is essential for nuclear pore integrity and maintenance of the pore selectivity filterCD-1 Simon Fraser University, University of British Columbia | Publication | 2014-10-01 | |
A mechanism-based GlcNAc -inspired cyclophellitol inactivator of the peptidoglycan recycling enzyme NagZ reverses resistance to $\upbeta$-lactams in Pseudomonas aeruginosa Simon Fraser University, University of Manitoba | Publication | 2018-09-01 | |
Pharmacological inhibition of O-GlcNAcase (OGA) enhances autophagy in brain through an mTOR-independent pathway. Simon Fraser University | Publication | 2018-02-01 | Yanping Zhu, Xiaoyang Shan, Farzaneh Safarpour, Nancy Erro Go, Nancy Li, Alice Shan, Mina Huang, Matthew Deen, Viktor Holicek, Roger Ashmus, Zarina Madden, Sharon Gorski, Michael Silverman, David Vocadlo |
A versatile fluorescence-quenched substrate for quantitative measurement of glucocerebrosidase activity within live cells.Loss of activity of the lysosomal glycosidase β-glucocerebrosidase (GCase) causes the lysosomal storage disease Gaucher disease (GD) and has emerged as the greatest genetic risk factor for the development of both Parkinson disease (PD) and dementia with Lewy bodies. There is significant interest into how GCase dysfunction contributes to these diseases, however, progress toward a full understanding is complicated by presence of endogenous cellular factors that influence lysosomal GCase activity. Indeed, such factors are thought to contribute to the high degree of variable penetrance of GBA mutations among patients. Robust methods to quantitatively measure GCase activity within lysosomes are therefore needed to advance research in this area, as well as to develop clinical assays to monitor disease progression and assess GCase-directed therapeutics. Here, we report a selective fluorescence-quenched substrate, LysoFQ-GBA, which enables measuring endogenous levels of lysosomal GCase activity within living cells. LysoFQ-GBA is a sensitive tool for studying chemical or genetic perturbations of GCase activity using either fluorescence microscopy or flow cytometry. We validate the quantitative nature of measurements made with LysoFQ-GBA using various cell types and demonstrate that it accurately reports on both target engagement by GCase inhibitors and the GBA allele status of cells. Furthermore, through comparisons of GD, PD, and control patient-derived tissues, we show there is a close correlation in the lysosomal GCase activity within monocytes, neuronal progenitor cells, and neurons. Accordingly, analysis of clinical blood samples using LysoFQ-GBA may provide a surrogate marker of lysosomal GCase activity in neuronal tissue.RG-1 Simon Fraser University | Publication | 2022-07-12 | |
Pharmacological Chaperones for GCase that Switch Conformation with pH Enhance Enzyme Levels in Gaucher Animal ModelsGaucher disease is a lysosomal storage disorder
caused by mutations which destabilize the native
folded form of GCase, triggering degradation and
ultimately resulting in low enzyme activity. Pharmacological
chaperones (PCs) which stabilize mutant GCase
have been used to increase lysosomal activity through
improving trafficking efficiency. By engineering their
inherent basicity, we have synthesized PCs that change
conformation between the ER and the lysosomal
environment, thus weakening binding to GCase after its
successful trafficking to the lysosome. NMR studies
confirmed the conformational change while X-ray data
reveal bound conformations and binding modes. These
results were further corroborated by cell studies showing
increases in GCase activity when using the pH-switchable
probe at low dosing. Preliminary in vivo assays with
humanized mouse models of Gaucher showed enhanced
GCase activity levels in relevant tissues, including the
brain, further supporting their potential.ID-04 University of Victoria, Simon Fraser University, University of British Columbia | Publication | 2022-07-21 | Andres Gonzalez-Santana, Kyle Robinson, Chelsea Vickers, Matthew Deen, Hong-Ming Chen, "Stephen Zhou ", Ben Dai, "Maria Fuller ", Alisdair B. Boraston, David Vocadlo, Lorne A. Clarke, Stephen G. Withers |
Quantifying lysosomal glycosidase activity within cells using bis-acetal substrates.Understanding the function and regulation of enzymes within their physiologically relevant milieu requires quality tools that report on their cellular activities. Here we describe a strategy for glycoside hydrolases that overcomes several limitations in the field, enabling quantitative monitoring of their activities within live cells. We detail the design and synthesis of bright and modularly assembled bis-acetal-based (BAB) fluorescence-quenched substrates, illustrating this strategy for sensitive quantitation of disease-relevant human α-galactosidase and α-N-acetylgalactosaminidase activities. We show that these substrates can be used within live patient cells to precisely measure the engagement of target enzymes by inhibitors and the efficiency of pharmacological chaperones, and highlight the importance of quantifying activity within cells using chemical perturbogens of cellular trafficking and lysosomal homeostasis. These BAB substrates should prove widely useful for interrogating the regulation of glycosidases within cells as well as in facilitating the development of therapeutics and diagnostics for this important class of enzymes.RG-1 University of Montreal, Simon Fraser University | Publication | 2022-02-24 | |
Quinolinic Acid Amyloid-like Fibrillar Assemblies Seed $\upalpha$-Synuclein Aggregation Simon Fraser University | Publication | 2018-08-01 | Omid Tavassoly, Dorin Sade, Santu Bera, Shira Shaham-Niv, David Vocadlo, Ehud Gazit |
Reduced protein O-glycosylation in the nervous system of the mutant SOD1 transgenic mouse model of amyotrophic lateral sclerosis Simon Fraser University, University of British Columbia | Publication | 2012-05-01 | |
Mislocalization of TDP-43 in the G93A mutant SOD1 transgenic mouse model of ALS Simon Fraser University, University of British Columbia | Publication | 2009-07-01 | |
The emerging link between O-GlcNAc and Alzheimer’s disease Simon Fraser University, University of British Columbia | Publication | 2014-10-01 | |
Pharmacological Inhibition of O-GlcNAcase (OGA) prevents cognitive decline and amyloid plaque formation in bigenic tau/APP mutant mice Simon Fraser University, University of British Columbia | Publication | 2014-10-01 | *Yuzwa SA, Xiaoyang Shan, Jones BA, Zhao G, Woodward ML, Li X, Yanping Zhu, *McEachern EJ, Silverman MA, Watson NV, Gong C-X, David Vocadlo |
Increasing O-GlcNAc slows neurodegeneration and stabilizes tau against aggregation Simon Fraser University, University of British Columbia | Publication | 2012-04-01 | *Yuzwa SA, Xiaoyang Shan, *Macauley MS, Clark T, Skorobogatko Y, Vosseller K, David Vocadlo |
Elevation of global O-GlcNAc in rodents using a selective O-GlcNAcase inhibitor does not cause insulin resistance or perturb glucohomeostasis Centre national de la recherche scientifique, Simon Fraser University, University of British Columbia | Publication | 2010-09-01 | *Macauley MS, Xiaoyang Shan, *Yuzwa SA, *Gloster TM, David Vocadlo |
A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo Simon Fraser University, University of British Columbia | Publication | 2008-08-01 | *Yuzwa SA, *Macauley MS, Heinonen JE, Xiaoyang Shan, Dennis RJ, *He Y, *Whitworth GE, *Stubbs KA, *McEachern EJ, Davies GJ, David Vocadlo |
Metabolic inhibitors of O-GlcNAc transferase (OGT) that act in vivo implicate decreased O-GlcNAc levels in leptin-mediated nutrient sensingCD-1 University of British Columbia - Okanagan, Simon Fraser University | Publication | 2018-05-01 | |
Molecular basis for the potent inhibition of the emerging carbapenemase VCC -1 by avibactam Simon Fraser University, University of Manitoba | Publication | 2019-02-01 | Chand S Mangat, Grishma Vadlamani, Viktor Holicek, Mitchell Chu, Veronica Larmour, David Vocadlo, Michael R Mulvey, Brian Mark |
Quantitating Organoleptic Volatile Phenols in Smoke-Exposed Vitis vinifera Berries University of British Columbia - Okanagan | Publication | 2017-09-01 | |
Expression, purification and preliminary crystallographic analysis of O-acetylhomoserine sulfhydrylase from Mycobacterium tuberculosis. | Publication | 2011-08-01 | Yin J, Garen CR, Bateman K, Yu M, Lyon EZ, Habel J, Hailey Kim, Hung LW, Kim CY, James MN |
The TB Structural Genomics Consortium: a decade of progress. | Publication | 2011-03-01 | Chim N, Habel JE, Johnston JM, Krieger I, Miallau L, Sankaranarayanan R, Morse RP, Bruning J, Swanson S, Hailey Kim, Kim CY, Li H, Bulloch EM, Payne RJ, Manos-Turvey A, Hung LW, Baker EN, Lott JS, James MN, Terwilliger TC, Eisenberg DS, Sacchettini JC, Goulding CW |
Cryo-EM structure provides insights into the dimer arrangement of the O-linked β-N-acetylglucosamine transferase OGT.The O-linked β-N-acetylglucosamine modification is a core signalling mechanism, with erroneous patterns leading to cancer and neurodegeneration. Although thousands of proteins are subject to this modification, only a single essential glycosyltransferase catalyses its installation, the O-GlcNAc transferase, OGT. Previous studies have provided truncated structures of OGT through X-ray crystallography, but the full-length protein has never been observed. Here, we report a 5.3 Å cryo-EM model of OGT. We show OGT is a dimer, providing a structural basis for how some X-linked intellectual disability mutations at the interface may contribute to disease. We observe that the catalytic section of OGT abuts a 13.5 tetratricopeptide repeat unit region and find the relative positioning of these sections deviate from the previously proposed, X-ray crystallography-based model. We also note that OGT exhibits considerable heterogeneity in tetratricopeptide repeat units N-terminal to the dimer interface with repercussions for how OGT binds protein ligands and partners.CD-1 Simon Fraser University | Publication | 2021-11-11 | "Richard Meek ", "James Blaza ", Jil Busmann, "Matthew Alteen ", David Vocadlo, "Gideon Davies " |
Potent De Novo Macrocyclic Peptides That Inhibit O-GlcNAc Transferase through an Allosteric Mechanism.Glycosyltransferases are a superfamily of enzymes that are notoriously difficult to inhibit. Here we apply an mRNA display technology integrated with genetic code reprogramming, referred to as the RaPID (random non-standard peptides integrated discovery) system, to identify macrocyclic peptides with high binding affinities for O-GlcNAc transferase (OGT). These macrocycles inhibit OGT activity through an allosteric mechanism that is driven by their binding to the tetratricopeptide repeats of OGT. Saturation mutagenesis in a maturation screen using 39 amino acids, including 22 non-canonical residues, led to an improved unnatural macrocycle that is ≈40 times more potent than the parent compound (Kiapp=1.5 nM). Subsequent derivatization delivered a biotinylated derivative that enabled one-step affinity purification of OGT from complex samples. The high potency and novel mechanism of action of these OGT ligands should enable new approaches to elucidate the specificity and regulation of OGT.CD-1 Simon Fraser University | Publication | 2022-12-02 | "Matthew Alteen ", "Hayden Peacock ", "Richard W. Meek ", Jil Busmann, Sha Zhu, "Gideon Davies ", "Hiroaki Suga ", David Vocadlo |
Organoaluminum-mediated interrupted nazarov reaction. | Publication | 2013-08-01 | Kwon Y, Rory McDonald, West FG |
Homologous Mukaiyama reactions via trapping of the Nazarov intermediate with silyloxyalkenes. | Publication | 2011-07-01 | Wu YK, Rory McDonald, West FG |
Expedient route to the tigliane-daphnane skeleton via oxonium ylide [1,2]-shift. | Publication | 2011-02-01 | Stewart C, Rory McDonald, West FG |
Concise route to triquinanes from pyran-2-ones. | Publication | 2008-09-01 | Li L, Rory McDonald, West FG |
Successful clinical treatment and functional immunological normalization of human MALT1 deficiency following hematopoietic stem cell transplantation. University of British Columbia | Publication | 2016-07-01 | Rozmus J, Rory McDonald, Fung SY, Del Bel KL, Roden J, Senger C, Kirk Schultz, McKinnon ML, Davis J, Turvey SE |
α-Hydroxycyclopentanones via one-pot oxidation of the trimethylaluminum-mediated Nazarov reaction with triplet oxygen. | Publication | 2014-04-01 | Kwon Y, Scadeng O, Rory McDonald, West FG |
How to make a difference: mechanisms of protein and nucleic acid modifying enzymes Simon Fraser University, University of British Columbia | Publication | 2012-12-01 | |
O-GlcNAc processing enzymes: catalytic mechanisms, substrate specificity, and enzyme regulation Simon Fraser University, University of British Columbia | Publication | 2012-12-01 | |
Mechanistic insights into glycosidase chemistry Simon Fraser University, University of British Columbia | Publication | 2008-10-01 | |
Detailed comparative analysis of the catalytic mechanisms of beta-N-acetylglucosaminidases from families 3 and 20 of glycoside hydrolases. Simon Fraser University, University of British Columbia | Publication | 2005-09-01 | |
The chemical synthesis of 2-deoxy-2-fluorodisaccharide probes of the hen egg white lysozyme mechanism. Simon Fraser University, University of British Columbia | Publication | 2005-02-01 | |
A strategy for functional proteomic analysis of glycosidase activity from cell lysates. Simon Fraser University | Publication | 2004-10-01 | |
A chemical approach for identifying O-GlcNAc-modified proteins in cells. University of California, Berkeley | Publication | 2003-08-01 | |
A case for reverse protonation: identification of Glu160 as an acid/base catalyst in Thermoanaerobacterium saccharolyticum beta-xylosidase and detailed kinetic analysis of a site-directed mutant. University of California, Berkeley, University of British Columbia | Publication | 2002-08-01 | |
Mechanism of Thermoanaerobacterium saccharolyticum beta-xylosidase: kinetic studies. University of California, Berkeley, University of British Columbia | Publication | 2002-08-01 | |
Catalysis by hen egg-white lysozyme proceeds via a covalent intermediate. Simon Fraser University, University of British Columbia | Publication | 2001-08-01 | |
Mechanism of action and identification of Asp242 as the catalytic nucleophile of Vibrio furnisii N-acetyl-beta-D-glucosaminidase using 2-acetamido-2-deoxy-5-fluoro-alpha-L-idopyranosyl fluoride. Simon Fraser University, University of British Columbia | Publication | 2000-01-01 | |
Identification of active site residues in glycosidases by use of tandem mass spectrometry. Simon Fraser University, University of British Columbia | Publication | 2000-01-01 | |
Identification of glu-277 as the catalytic nucleophile of Thermoanaerobacterium saccharolyticum beta-xylosidase using electrospray MS. Simon Fraser University, University of British Columbia | Publication | 1998-10-01 | |
O-GlcNAc and neurodegeneration: biochemical mechanisms and potential roles in Alzheimer's disease and beyond Simon Fraser University, University of British Columbia | Publication | 2014-04-01 | |
Reports from the award symposia hosted by the American Chemical Society Division of Carbohydrate Chemistry at the 245th American Chemical Society National Meeting Simon Fraser University, University of British Columbia | Publication | 2013-07-01 | |
Tools for probing and perturbing O-GlcNAc in cells and in vivoCD-1 Simon Fraser University, University of British Columbia | Publication | 2013-07-01 | |
Hyper-O-GlcNAcylation is anti-apoptotic and maintains constitutive NF-κB activity in pancreatic cancer cells Simon Fraser University, University of British Columbia | Publication | 2013-05-01 | |
Developing inhibitors of glycan processing enzymes as tools for enabling glycobiology Simon Fraser University, University of British Columbia | Publication | 2012-07-01 | |
Providing β-lactams a helping hand: targeting the AmpC β-lactamase induction pathway Simon Fraser University, University of British Columbia | Publication | 2011-12-01 | |
Increasing O-GlcNAc levels: an overview of small-molecule inhibitors of O-GlcNAcase Simon Fraser University, University of British Columbia | Publication | 2010-02-01 | |
Mechanism, structure, and inhibition of O-GlcNAc Processing Enzymes Simon Fraser University, University of British Columbia | Publication | 2010-01-01 | |
O-GlcNAc modification and the tauopathies: insights from chemical biology Simon Fraser University, University of British Columbia | Publication | 2009-10-01 | |
Enzymatic characterization and inhibition of the nuclear variant of human O-GlcNAcase Simon Fraser University, University of British Columbia | Publication | 2009-06-01 | |
Affinity-based proteomics probes; tools for studying carbohydrate-processing enzymes Simon Fraser University, University of British Columbia | Publication | 2009-03-01 | |
Characterization of a beta-N-acetylhexosaminidase and a beta-N-acetylglucosaminidase/beta-glucosidase from Cellulomonas fimi. Simon Fraser University, University of British Columbia | Publication | 2006-07-01 | |
Functional proteomic profiling of glycan-processing enzymes. Simon Fraser University | Publication | 2006-01-01 | |
Biochemical and structural assessment of the 1-N-azasugar GalNAc-isofagomine as a potent family 20 beta-N-acetylhexosaminidase inhibitor. Simon Fraser University, University of British Columbia | Publication | 2001-11-01 | |
Crystallographic evidence for substrate-assisted catalysis in a bacterial beta-hexosaminidase. Simon Fraser University, University of British Columbia | Publication | 2001-03-01 | |
Characterization of the Glu and Asp residues in the active site of human beta-hexosaminidase B. Simon Fraser University, University of British Columbia | Publication | 2001-02-01 | |
Role of beta Arg211 in the active site of human beta-hexosaminidase B. Simon Fraser University, University of British Columbia | Publication | 2000-05-01 | |
Structural, mechanistic, and computational analysis of the effects of anomeric fluorines on anomeric fluoride departure in 5-fluoroxylosyl fluorides Simon Fraser University, University of British Columbia | Publication | 2011-10-01 | |
Streptococcus pneumoniae endohexosaminidase D, structural and mechanistic insight into substrate-assisted catalysis in family 85 glycoside hydrolases Simon Fraser University, University of British Columbia, University of Victoria | Publication | 2009-04-01 | |
A selective inhibitor Gal-PUGNAc of human lysosomal beta-hexosaminidases modulates levels of the ganglioside GM2 in neuroblastoma cells Simon Fraser University, University of British Columbia | Publication | 2009-01-01 | |
The synthesis and biological evaluation of some carbocyclic analogues of PUGNAc Simon Fraser University, University of British Columbia | Publication | 2008-11-01 | |
A highly concise preparation of O-deacetylated arylthioglycosides of N-acetyl-D-glucosamine from 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-alpha-D-glucopyranosyl chloride and aryl thiols or disulfides. Simon Fraser University | Publication | 2006-07-01 | |
A divergent synthesis of 2-acyl derivatives of PUGNAc yields selective inhibitors of O-GlcNAcase. Simon Fraser University | Publication | 2006-03-01 | |
O-GlcNAcase catalyzes cleavage of thioglycosides without general acid catalysis. Simon Fraser University | Publication | 2005-12-01 | |
Aspartate 313 in the Streptomyces plicatus hexosaminidase plays a critical role in substrate-assisted catalysis by orienting the 2-acetamido group and stabilizing the transition state. University of California, Berkeley, University of British Columbia | Publication | 2002-10-01 | |
The chitopentaose complex of a mutant hen-egg white lysozyme displays no distortion of the –1 sugar away from a 4C1 chair conformation University of British Columbia, Simon Fraser University | Publication | 2009-06-01 | |
Inhibition of the family 20 glycoside hydrolase catalytic modules in the Streptococcus pneumoniae exo-β-D-N-acetylglucosaminidase, StrH. Simon Fraser University, University of British Columbia, University of Victoria | Publication | 2013-12-01 | |
Inhibition of the family 20 glycoside hydrolase catalytic modules in the Streptococcus pneumoniae exo-β-d-N-acetylglucosaminidase, StrH Simon Fraser University, University of British Columbia, University of Victoria | Publication | 2013-12-01 | |
Active site plasticity within the glycoside hydrolase NagZ underlies a dynamic mechanism of substrate distortion Simon Fraser University, University of British Columbia | Publication | 2012-11-01 | |
Metabolic inhibition of sialyl-lewis x biosynthesis by 5-thiofucose remodels the cell surface and impairs selectin-mediated cell adhesion Simon Fraser University, University of British Columbia | Publication | 2012-11-01 | |
Insights into O-linked N-acetylglucosamine (O-GlcNAc) processing and dynamics through kinetic analysis of O-GlcNAc transferase and O-GlcNAcase activity on protein substrates Simon Fraser University, University of British Columbia | Publication | 2012-05-01 | |
Analysis of keystone enzyme in Agar hydrolysis provides insight into the degradation (of a polysaccharide from) red seaweeds Simon Fraser University, University of British Columbia, University of Victoria | Publication | 2012-04-01 | |
6''-Azido-6''-deoxy-UDP-N-acetylglucosamine as a glycosyltransferase substrate Centre national de la recherche scientifique, Simon Fraser University, University of British Columbia | Publication | 2011-02-01 | |
Streptococcus pneumoniae endohexosaminidase D; feasibility of using N-glycan oxazoline donors for synthetic glycosylation of a GlcNAc-asparagine acceptor University of Victoria, Simon Fraser University, University of British Columbia | Publication | 2010-04-01 | |
Mammalian Notch is modified by D-Xyl-alpha1-3-D-Xyl-alpha1-3-D-Glc-beta1-O-Ser: implementation of a method to study O-glucosylation Simon Fraser University, University of British Columbia | Publication | 2010-03-01 | |
Visualizing the reaction coordinate of an O-GlcNAc hydrolase Simon Fraser University, University of British Columbia | Publication | 2010-02-01 | |
Probing synergy between two catalytic strategies in the glycoside hydrolase O-GlcNAcase using multiple linear free energy relationships Simon Fraser University, University of British Columbia | Publication | 2009-09-01 | |
Inactivation of the glycoside hydrolase NagZ attenuates antipseudomonal beta-lactam resistance in Pseudomonas aeruginosa Simon Fraser University, University of British Columbia | Publication | 2009-06-01 | |
O-GLcNAc post-translational modifications regulate the entry of neurons into an axon branching program Simon Fraser University, University of British Columbia | Publication | 2009-01-01 | Francisco H, Kollins K, Varghis N, David Vocadlo, Vosseller K, Gallo G |
Structural and mechanistic insight into the basis of mucopolysaccharidosis IIIB Simon Fraser University, University of Victoria | Publication | 2008-05-01 | |
Small molecule inhibitors of a glycoside hydrolase attenuate inducible AmpC-mediated beta-lactam resistance. Simon Fraser University | Publication | 2007-07-01 | |
Software for rapid time dependent ChIP -sequencing analysis (TDCA) Simon Fraser University | Publication | 2017-11-01 | Mike Myschyshyn, Marco Farren-Dai, Tien-Jui Chuang, David Vocadlo |
A Chemical Genetic Method for Monitoring Genome-Wide Dynamics of O-GlcNAc Turnover on Chromatin-Associated Proteins Simon Fraser University | Publication | 2019-03-01 | |
O-GlcNAc Modification of tau Directly Inhibits Its Aggregation without Perturbing the Conformational Properties of tau Monomers Simon Fraser University, University of British Columbia | Publication | 2014-01-01 | |
Conformational itinerary of Pseudomonas aeruginosa 1,6-Anhydro-N-acetylmuramic acid kinase during its catalytic cycle Simon Fraser University, University of British Columbia | Publication | 2013-12-01 | Bacik JP, Tavassoli M, Patel TR, McKenna SA, David Vocadlo, Khajehpour M, Mark BL |
Metabolism of vertebrate amino sugars with N-glycolyl groups: incorporation of N-glycolylhexosamines into mammalian glycans by feeding N-glycolylgalactosamine Simon Fraser University, University of British Columbia | Publication | 2012-08-01 | Bergfeld AK, Pearce OM, Diaz SL, Lawrence R, David Vocadlo, Choudhury B, Esko JD, Ajit Varki |
Crystal structure of the AmpR effector binding domain provides insight into the molecular regulation of inducible ampc beta-lactamase Simon Fraser University, University of British Columbia | Publication | 2010-07-01 | Balcewich MD, Reeve TM, Orlikow EA, Donald LJ, David Vocadlo, Mark BL |
Elevation of global O-GlcNAc levels in 3T3-L1 adipocytes by selective inhibition of O-GlcNAcase does not induce insulin resistance Simon Fraser University, University of British Columbia | Publication | 2008-12-01 | *Macauley MS, Bubb AK, Martinez-Fleites C, Davies GJ, David Vocadlo |
Structure of an O-GlcNAc transferase homolog provides insight into intracellular glycosylation Simon Fraser University | Publication | 2008-07-01 | Martinez-Fleites C, *Macauley MS, *He Y, *Shen DL, David Vocadlo, Davies GJ |
Inhibition of O-GlcNAcase by a gluco-configured nagstatin and a PUGNAc-imidazole hybrid inhibitor. Simon Fraser University | Publication | 2006-11-01 | Shanmugasundaram B, Debowski AW, Dennis RJ, Davies GJ, David Vocadlo, Vasella A |
Identification of Asp174 and Asp175 as the key catalytic residues of human O-GlcNAcase by functional analysis of site-directed mutants. Simon Fraser University | Publication | 2006-03-01 | |
Molecular basis for G protein control of the prokaryotic ATP sulfurylase. Simon Fraser University | Publication | 2006-01-01 | Mougous JD, Lee DH, Hubbard SC, Schelle MW, David Vocadlo, Berger JM, Bertozzi CR |
O-GlcNAcase uses substrate-assisted catalysis: kinetic analysis and development of highly selective mechanism-inspired inhibitors. Simon Fraser University | Publication | 2005-07-01 | |
sp2-Iminosugars targeting human lysosomal β-hexosaminidase as pharmacological chaperone candidates for late-onset Tay-Sachs disease.Other Simon Fraser University | Publication | 2022-05-16 | "Manuel González-Cuesta ", "Irene Herrera-González ", "M. Isabel García-Moreno ", Roger Ashmus, David Vocadlo, "José M. García Fernández ", "Eiji Nanba ", "Katsumi Higaki ", "Carmen Ortiz Mellet " |
The development of selective inhibitors of NagZ: increased susceptibility of gram-negative bacteria to β-Lactams Simon Fraser University, University of British Columbia | Publication | 2013-10-01 | *Stubbs KA, Bacik JP, *Perley-Robertson GE, *Whitworth GE, *Gloster TM, David Vocadlo, Mark BL |
Structural snapshots of the reaction coordinate for O-GlcNAc transferase Simon Fraser University, University of British Columbia | Publication | 2012-12-01 | |
AmpG inactivation restores susceptibility of pan-beta-lactam-resistant Pseudomonas aeruginosa clinical strains Centre national de la recherche scientifique, Simon Fraser University, University of British Columbia | Publication | 2011-05-01 | Zamorano L, Reeve TM, Juan C, Moyá B, Cabot G, David Vocadlo, Mark BL, Oliver A |
Analysis of a new family of widely distributed metal-independent alpha-mannosidases provides unique insight into the processing of N-linked glycans Simon Fraser University, Centre national de la recherche scientifique, University of British Columbia, University of Victoria | Publication | 2011-04-01 | |
Mapping O-GlcNAc modification sites on tau and generation of a site-specific O-GlcNAc tau antibody Centre national de la recherche scientifique, Simon Fraser University, University of British Columbia | Publication | 2011-03-01 | *Yuzwa SA, *Yadav AK, Skorobogatko Y, Clark T, Vosseller K, David Vocadlo |
Hijacking a biosynthetic pathway yields a glycosyltransferase inhibitor within cells Simon Fraser University, Centre national de la recherche scientifique, University of British Columbia | Publication | 2011-03-01 | |
Inhibition of O-GlcNAcase using a potent and cell-permeable inhibitor does not induce insulin resistance in 3T3-L1 adipocytes Centre national de la recherche scientifique, Simon Fraser University, University of British Columbia | Publication | 2010-09-01 | *Macauley MS, *He Y, *Gloster TM, *Stubbs KA, Davies GJ, David Vocadlo |
Drosophila O-GlcNAc transferase (OGT) is encoded by the Polycomb group (PcG) gene, super sex combs (sxc) Simon Fraser University, University of British Columbia | Publication | 2009-08-01 | Sinclair DA, Syrzycka M, *Macauley MS, Rastgardani T, Komljenovic I, David Vocadlo, Brock HW, Honda BM |
Insight into a strategy for attenuating AmpC-mediated beta-lactam resistance: structural basis for selective inhibition of the glycoside hydrolase NagZ Simon Fraser University, University of British Columbia | Publication | 2009-07-01 | Balcewich MD, *Stubbs KA, *He Y, James TW, Davies GJ, David Vocadlo, Mark BL |
In vivo modulation of O-GlcNAc levels regulates hippocampal synaptic plasticity through interplay with phosphorylation Simon Fraser University, University of British Columbia | Publication | 2009-01-01 | Tallent MK, Varghis N, Skorobogatko Y, Hernandez-Cuebas L, Whelan K, David Vocadlo, Vosseller K |
Synthesis and use of mechanism-based protein-profiling probes for retaining beta-D-glucosaminidases facilitate identification of Pseudomonas aeruginosa NagZ Simon Fraser University | Publication | 2008-01-01 | *Stubbs KA, Scaffidi A, Debowski AW, Mark BL, Stick RV, David Vocadlo |
A 1-acetamido derivative of 6-epi-valienamine: an inhibitor of a diverse group of beta-N-acetylglucosaminidases. Simon Fraser University | Publication | 2007-09-01 | Scaffidi A, Stubbs KA, Dennis RJ, Taylor EJ, Davies GJ, David Vocadlo, Stick RV |
Essential role of O-GlcNAcylation in stabilization of oncogenic factors Simon Fraser University | Publication | 2019-04-01 | Vivek Makwana, Philip Ryan, Bhautikkumar Patel, Matt Alteen, Shailendra-Anoopkumar Dukie, David Vocadlo, Santosh Rudrawar |
O-GlcNAcylation regulates cancer metabolism 1 and survival stress signaling via regulation of HIF-1 pathway Simon Fraser University, University of British Columbia | Publication | 2014-06-01 | Ferrer CM, Lynch TP, Sodi VL, Falcone JN, Schwab LP, Peacock DL, David Vocadlo, Seagroves TN, Reginato MJ |
HCF-1 is cleaved in the active site of O-GlcNAc transferase Simon Fraser University, University of British Columbia | Publication | 2013-12-01 | |
Synthesis of 4-methylumbelliferyl α-d-mannopyranosyl-(1→6)-β-d-mannopyranoside and development of a coupled fluorescent assay for GH125 exo-α-1,6-mannosidases Simon Fraser University, University of Victoria, University of British Columbia | Publication | 2013-08-01 | |
Molecular basis of 1,6-anhydro bond cleavage and phosphoryl transfer by Pseudomonas aeruginosa 1,6-anhydro-N-acetylmuramic acid kinase Centre national de la recherche scientifique, Simon Fraser University, University of British Columbia | Publication | 2011-04-01 | Bacik JP, *Whitworth GE, *Stubbs KA, *Yadav AK, Martin DR, Bailey-Elkin BA, David Vocadlo, Mark BL |
NagZ inactivation prevents and reverts beta-lactam resistance, driven by AmpD and PBP 4 mutations, in Pseudomonas aeruginosa Centre national de la recherche scientifique, Simon Fraser University, University of British Columbia | Publication | 2010-09-01 | Zamorano L, Reeve TM, Deng L, Juan C, Moyá B, Cabot G, David Vocadlo, Mark BL, Oliver A |
Differential recognition and hydrolysis of host carbohydrate antigens by Streptococcus pneumoniae family 98 glycoside hydrolases Simon Fraser University, University of British Columbia, University of Victoria | Publication | 2009-09-01 | |
Molecular basis for inhibition of GH84 glycoside hydrolases by substituted azepanes: conformational flexibility enables probing of substrate distortion Simon Fraser University, University of British Columbia | Publication | 2009-04-01 | Marcelo F, *He Y, *Yuzwa SA, Nieto L, Jiménez-Barbero J, Sollogoub M, David Vocadlo, Davies GD, Blériot Y |
Functional analysis of a group A streptococcal glycoside hydrolase Spy1600 from family 84 reveals it is a beta-N-acetylglucosaminidase and not a hyaluronidase. Simon Fraser University | Publication | 2006-10-01 | Sheldon WL, Macauley MS, Taylor EJ, Robinson CE, Charnock SJ, Davies GJ, David Vocadlo, Black GW |
Immunoprecipitation and Western blot-based detection of protein O-GlcNAcylation in cells.Other Simon Fraser University | Publication | 2022-03-18 | "Oumaima Ahmed ", "Malik Affar ", "Louis Masclef ", "Mohamed Echbicheb ", "Mila Gushul-Leclaire ", "Benjamin Estavoyer ", David Vocadlo, "El Bachir Affar " |
Selective trihydroxyazepane NagZ inhibitors increase sensitivity of Pseudomonas aeruginosa to β-lactams Simon Fraser University, University of British Columbia | Publication | 2013-10-01 | Mondon M, *Hur S, Vadlamani G, Rodrigues P, Tsybina P, Oliver A, Mark BL, David Vocadlo, Blériot Y |
Analysis of PUGNAc and NAG-thiazoline as transition state analogues for human O-GlcNAcase: mechanistic and structural insights into inhibitor selectivity and transition state poise. Simon Fraser University | Publication | 2007-01-01 | Whitworth GE, Macauley MS, Stubbs KA, Dennis RJ, Taylor EJ, Davies GJ, Greig IR, David Vocadlo |
Structure and mechanism of a bacterial beta-glucosaminidase having O-GlcNAcase activity. Simon Fraser University | Publication | 2006-04-01 | Dennis RJ, Taylor EJ, Macauley MS, Stubbs KA, Turkenburg JP, Hart SJ, Black GN, David Vocadlo, Davies GJ |
Discovery of a New Drug-like Series of OGT Inhibitors by Virtual Screening.Other Simon Fraser University | Publication | 2022-05-23 | "Elena M. Loi ", "Tihomir Tomašič ", "Cyril Balsollier ", "Kevin van Eekelen ", "Matjaž Weiss ", "Martina Gobec ", "Matthew G. Alteen ", David Vocadlo, "Roland Pieters ", "Marko Anderluh " |
Inhibition of the pneumococcal virulence factor StrH and molecular insights into N-glycan recognition and hydrolysis Simon Fraser University, University of British Columbia, University of Victoria | Publication | 2011-11-01 | Benjamin Pluvinage, Higgins MA, Abbott DW, Robb C, Dalia AB, *Deng L, Weiser JN, Parsons TB, Fairbanks AJ, David Vocadlo, Alisdair B. Boraston |
Cytoplasmic O-GlcNAcylation occurs cotranslationally to stabilize nascent polypeptide chains. Simon Fraser University, University of British Columbia | Publication | 2015-02-01 | Zhu, Y , * Liu, T W , * Eskandari, R , * Zandberg, W , * Cecioni, S , David Vocadlo |
Substrate-guided front-face reaction revealed by combined structural snapshots and metadynamics for the polypeptide N-Acetylgalactosaminyltransferase 2 Simon Fraser University, University of British Columbia | Publication | 2014-06-01 | Lira-Navarrete E, Iglesias-Fernández J, Wesley F. Zandberg, Compañón I, Kong Y, Corzana, F, Pinto BM, Clausen H, Peregrina JM, David Vocadlo, Rovira C, Hurtado-Guerrero R |
Metabolism of vertebrate amino sugars with N-glycolyl groups: intracellular β-O-linked N-glycolylglucosamine (GlcNGc), UDP-GlcNGc, and the biochemical and structural rationale for the substrate tolerance of β-O-linked β-N-acetylglucosaminidase Simon Fraser University, University of British Columbia | Publication | 2012-08-01 | *Macauley MS, Chan J, Wesley F. Zandberg, *He Y, *Whitworth GE, *Stubbs KA, *Yuzwa SA, Bennet AJ, Ajit Varki, Davies GJ, David Vocadlo |
Crystal structure of beta-D-xylosidase from Thermoanaerobacterium saccharolyticum, a family 39 glycoside hydrolase. Simon Fraser University, University of British Columbia | Publication | 2004-01-01 | Yang JK, Yoon HJ, Ahn HJ, Lee BI, Pedelacq JD, Liong EC, Berendzen J, Laivenieks M, Vieille C, Zeikus GJ, David Vocadlo, Stephen G. Withers, Suh SW |
The conformation and function of a multimodular glycogen-degrading pneumococcal virulence factor Centre national de la recherche scientifique, Simon Fraser University, University of British Columbia, University of Victoria | Publication | 2011-05-01 | Lammerts van Bueren A, Ficko-Blean E, Benjamin Pluvinage, Hehemann JH, Higgins MA, *Deng L, Ogunniyi AD, Stroeher UH, El Warry N, Burke RD, Czjzek M, Paton JC, David Vocadlo, Alisdair B. Boraston |