A5045975703- Carbohydrate Chemistry and Synthesis
- Enzyme Production and Characterization
- Glycosylation and Glycoproteins Research
- Legume Nitrogen Fixing Symbiosis
- Studies on Chitinases and Chitosanases
- Biofuel production and bioconversion
- Enzyme Catalysis and Immobilization
- Microbial Metabolites in Food Biotechnology
- Sinusitis and nasal conditions
- Head and Neck Surgical Oncology
- Zeolite Catalysis and Synthesis
- Polysaccharides and Plant Cell Walls
- Cancer Genomics and Diagnostics
- Chemical Looping and Thermochemical Processes
- Healthcare Operations and Scheduling Optimization
- Genomic variations and chromosomal abnormalities
- Meningioma and schwannoma management
- Health Systems, Economic Evaluations, Quality of Life
- Human Health and Disease
- Bacterial biofilms and quorum sensing
- Biomarkers in Disease Mechanisms
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Synthesis and bioactivity of alkaloids
- Reproductive Health and Technologies
- Chronic Myeloid Leukemia Treatments
Provincial Health Services Authority
2020-2023
University of British Columbia
1999-2013
University of Copenhagen
2005
Lund University
2000-2005
University of Colorado Boulder
1974
We analysed primary breast cancers by genomic DNA copy number arrays, methylation, exome sequencing, messenger RNA microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression subtypes demonstrated the existence of four main cancer classes when combining data from five platforms, each which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA...
Many mutations that contribute to the pathogenesis of acute myeloid leukemia (AML) are undefined. The relationships between patterns and epigenetic phenotypes not yet clear. We analyzed genomes 200 clinically annotated adult cases de novo AML, using either whole-genome sequencing (50 cases) or whole-exome (150 cases), along with RNA microRNA DNA-methylation analysis. AML have fewer than most other cancers, an average only 13 found in genes. Of these, 5 genes recurrently mutated AML. A total...
The conformational reaction pathway for β-mannosidases proposed here is distinct from that of glucosidases and cellulases. proposal based on substrate distortions along the a β-mannosidase (see picture) were revealed by X-ray crystallography are close in space to known inhibitors.
Engineering enzymes: The glutamic acid nucleophile of a retaining β-mannosidase has been replaced with serine residue to form β-mannosynthase. When the new enzyme is provided an α-mannosyl fluoride donor and appropriate acceptor, β-mannoside linkages are synthesized (see scheme). Remarkably, can be generated in situ by providing mannosynthase excess ion. Supporting information for this article available on WWW under http://www.angewandte.com or from author. Please note: publisher not...
ADVERTISEMENT RETURN TO ISSUEPREVFeatureNEXTPeer Reviewed: Zirconia Stationary Phases for Extreme SeparationsComposite materials surpass standard silicon and carbon stability robustness in complicated reversed-phase column applications.Christopher J. Dunlap, Peter W. Carr, Clayton V. McNeff, Dwight StollCite this: Anal. Chem. 2001, 73, 21, 598 A–607 APublication Date (Web):November 1, 2001Publication History Published online1 November 2001Published inissue 1...
Abstract Six women presented with the clinical picture of essential thrombocythemia (ET) without anemia, marked splenomegaly, and extreme leukocytosis characteristic chronic myelogenous leukemia (CML). All had Philadelphia chromosome on karyotype analysis bone marrow. Peripheral basophilia was present in four cases, providing a clue that might be present. Marrow biopsy showed granulocytic hyperplasia either small megakaryocytes or sheets atypia, findings are more typical CML than ET. The...
Mutant endo-mannanases, in which the catalytic nucleophile has been replaced, function as glycosynthases synthesis of manno-oligosaccharides defined lengths.
The endo-β-1,4-mannanase from the soil bacterium Cellulomonas fimi is a modular plant cell wall degrading enzyme involved in hydrolysis of backbone mannan, one most abundant polysaccharides hemicellulosic network wall. crystal structure recombinant truncated C. (CfMan26A-50K) was determined by X-ray crystallography to 2.25 Å resolution using molecular replacement technique. overall consists core (β/α)8-barrel catalytic module characteristic clan GH-A, connected via linker an...
The Gram‐positive soil bacterium Cellulomonas fimi is shown to produce at least two intracellular β‐ N ‐acetylglucosaminidases, a family 20 ‐acetylhexosaminidase (Hex20), and novel 3‐β‐ ‐acetylglucosaminidase/β‐glucosidase (Nag3), through screening of genomic expression library, cloning genes analysis their sequences. Nag3 exhibits broad substrate specificity for substituents the C2 position glycone: k cat / K m values 25 °C were 0.066 s −1 ·m 0.076 4′‐nitrophenyl ‐acetyl‐ d ‐glucosaminide...
The genes man26a and man2A from Cellulomonas fimi encode mannanase 26A (Man26A) beta-mannosidase 2A (Man2A), respectively. Mature Man26A is a secreted, modular protein of 951 amino acids, comprising catalytic module in family 26 glycosyl hydrolases, an S-layer homology module, two modules unknown function. Exposure produced by Escherichia coli to C. protease generates active fragments the enzyme that correspond polypeptides with activity during growth on mannans, indicating it may be only...
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTEnzymatic Synthesis of Carbon−Fluorine BondsDavid L. Zechel, Stephen P. Reid, Oyekanmi Nashiru, Christoph Mayer, Dominik Stoll, David Jakeman, R. Antony J. Warren, and G. WithersView Author Information Protein Engineering Network Centres Excellence Departments Chemistry Microbiology University British Columbia Vancouver, B.C., Canada V6T 1Z1 Cite this: Am. Chem. Soc. 2001, 123, 18, 4350–4351Publication Date (Web):April 13, 2001Publication...
The chemical mechanism of a retaining β-mannosidase from Cellulomonas fimi has been characterized through steady-state kinetic analyses with range substrates, coupled rescue studies on both the wild-type enzyme and mutants in which active site carboxyl groups have replaced. Studies series aryl β-mannosides vastly different reactivities (pKalg = 4−10) allowed isolation glycosylation deglycosylation steps. Substrate inhibition was observed for all but least reactive these substrates. Brønsted...
A modular mannanase (Man26A) from the bacterium Cellulomonas fimi contains a mannan-binding module (Man26Abm) that binds to soluble but not insoluble mannans. Man26Abm does bind cellulose, chitin or xylan. The Kd for binding of locust bean gum (LBG) is ∼0.2 μM. Man26A first reported contain module.
Incubation of the β-mannosidase Man2A from Cellulomonas fimi with 2-deoxy-2-fluoro-β-d-mannosyl fluoride (2FManβF) resulted in time-dependent inactivation enzyme (inactivation rate constant ki = 0.57min-1, dissociation for inactivator Ki 0.41mM) through accumulation a covalent 2-deoxy-2-fluoro-α-d-mannosyl–β-mannosidase 2A (2FMan–Man2A) intermediate, as observed by electrospray ionization mass spectrometry. The stoichiometry was 1:1. Removal excess and regeneration active transglycosylation...
Maßgeschneiderte Enzyme: Der Glutaminsäurerest einer β-Mannosidase wurde durch einen Serinrest ersetzt, woraus eine β-Mannosynthase resultierte. Bietet man diesem Enzym α-Mannosylfluorid-Donor und passenden Acceptor als Substrate an, erhält β-Mannosidverknüpfungen (siehe Schema). Durch Zugabe von Fluoridionen im Überschuss kann das α-Mannosylfluorid in situ gebildet werden.
Der konformative Reaktionspfad, der hier für β-Mannosidasen vorgeschlagen wird, unterscheidet sich von dem Glucosidasen und Cellulasen. Vorschlag beruht auf Substratverzerrungen entlang Reaktionspfad einer β-Mannosidase (siehe Bild), die röntgenographisch nachgewiesen wurden Konformationsraum bekannter β-Mannosidase-Inhibitoren nahestehen.
Endo–1,4-β-mannanases (β-mannanases) randomly hydrolyse the mannosidic bonds within main chain of various mannans and heteromannans. Some these polysaccharides are hemicelluloses, a major part plant cell-wall. The β-mannanases have been assigned to family 5 26 glycoside hydrolase clan A. This work presents detailed kinetic analysis β-mannanase CfMan26A from soil-bacterium Cellulomonas fimi. full-length enzyme consists five modules: catalytic module, an immunoglobulin-like mannan-binding...
Incubation of the β-mannosidase Man2A from Cellulomonas fimi with 2-deoxy-2-fluoro-β-d-mannosyl fluoride (2FManβF) resulted in time-dependent inactivation enzyme (inactivation rate constant ki = 0.57min-1, dissociation for inactivator Ki 0.41mM) through accumulation a covalent 2-deoxy-2-fluoro-α-d-mannosyl–β-mannosidase 2A (2FMan–Man2A) intermediate, as observed by electrospray ionization mass spectrometry. The stoichiometry was 1:1. Removal excess and regeneration active transglycosylation...
Following onset of the COVID-19 pandemic, chronic kidney disease (CKD) clinics in BC shifted from established methods mostly in-person care delivery to virtual (VC) and thereafter a hybrid two.To determine strengths, weaknesses, quality-of-care delivery, key considerations associated with VC usage inform optimal way(s) integrating traditional multidisciplinary clinics.Qualitative evaluation.British Columbia, Canada.Patients health providers clinics.Development semi-structured interviews...
Background: Multidisciplinary care of patients with chronic kidney disease (CKD) as it previously existed was predicated on an evidence and experience base improved patient outcomes within established well-described service delivery model. The onset the COVID-19 pandemic brought a departure from this model toward integration virtual in-person care. Objective: To develop evaluation framework to determine whether shift in models has affected quality multidisciplinary and/or patient-clinician...
Cellulomonas fimi genomic DNA was digested with HpaI, MunI, HindIII, and NsiI, producing fragments ranging in size from 20 to 1400 kbp that were resolved by pulsed field gel electrophoresis. Genetic physical linkages determined Southern blotting used construct a genome map. has single circular chromosome of approx. 4000 kbp. Except for two closely linked genes, cbh6A cel5A, the genes known encode glycoside hydrolases are scattered widely on chromosome.Key words: fimi, map, electrophoresis,...