Global ETD Search
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Showing 1 to 17 of 17 for “"UDP-GlcNAc"”.
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Structural and Functional Characterization of B. Anthracis Udp-Glcnac 2-Epimerase and Salmonella Secreted Effector I
… study of the Bacillus anthracis cell-wall enzyme UDP-GlcNAc 2-Epimerase and the Salmonella secreted virulence effector SseI. UDP-GlcNAc 2-Epimerase is an essential B. anthracis enzyme required for formation of the peptidoglycan cell wall precursor UDP-ManAc. We have solved the epimerase's crystal …
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Investigation of asparagine-linked glycosylation in archaeal and bacterial systems
… a robust synthesis of the highly modified UDP-GlcNAc(3NAc)A and thus turned to the Wbp pathway from the opportunistic pathogen Pseudomonas aeruginosa. Early genetic studies suggested that P. aeruginosa produces UDP-GlcNAc(3NAc)A as a precursor to ManNAc(3NAc)A, a carbohydrate found in the …
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Synthesis and evaluation of M.tb Glycosyltransferase (MshA) inhibitors
… molecules that are expected to compete for the UDP-GlcNAc binding site of the glycosyltransferase (MshA) of M.tb. The bioactivity of the designed molecules against M.tb in cell free and whole cell assays serves as a basis for further inhibitor optimisation. Amongst the thiazolidinethione …
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Investigating the role of the UDP-galactose transporter SLC35A2 in the regulation of HIF signalling
… of HIF is of intense interest. The Golgi UDP-galactose transporter SLC35A2 was identified by the Ashcroft group as a novel regulator of HIF-α, and CHO cells that had lost SLC35A2 exhibited elevated HIF-α protein in normoxia. It is known that the absence of SLC35A2 in the Golgi leads to …
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Study of the Dynamics of Retaining GT-B Fold Glycosyltransferases Using Hydrogen Deuterium Exchange Mass Spectrometry
… uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc), dynamics decrease inboth domain halves. Identical deuterium uptake plots at the NTD with I1P or UDP-GlcNAcsuggest that UDP-GlcNAc binding creates the binding site for I1P. Surprisingly, UDP bindingresults in diminished dynamics in most …
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Investigating the role of UDP-<i>N</i>-acetylhexosamine pyrophosphorylases in regulating <i>O</i>-GlcNAcylation in human disease
… O-linked N-acetyl-β-<sub>D</sub>glucosamine (O-GlcNAc) was first observed on the surface of lymphocytes in 1984. It was then found that over 1,000 nucleocytoplasmic proteins are modified by O-GlcNAc (O-GlcNAcylation). Interestingly, O-GlcNAc homeostasis is regulated by a single pair of enzymes: …
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Targeting final steps of sugar nucleotide biosynthetic pathway against <i>Aspergillus fumigatus</i>
… synthase that synthesize β-1,3 glucan from UDP-Glc. Although inhibitors of other glycosyltransferases (e.g. chitin synthases) also exhibit antifungal activity, only echinocandins have been approved for the treatment of aspergillosis. This is due to intrinsic drawbacks of targeting …
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Biochemical characterization of Cj 1123 c, a putative acetyltransferase & Cj 1319, a putative C6 dehydratase from Campylobacter jejuni.
… that Cjll23c is responsible for the synthesis of UDP- diacetamidobacillosamine. We also show that Cj 1123c can N-acetylate the O- glycosylation pathway intermediate, UDP-4-amino-4,6-dideoxy-AltNAc, accommodate different acyl donors and O-acetylate UDP-GlcNAc, thereby generating novel sugars. We …
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Investigation of the antibacterial activity and the biosynthesis gene cluster of the peptide antibiotic feglymycin
… das Feglymycin die Enzyme MurA (Enopyruvyl-UDP-GlcNAc Synthase) und MurC (UDP-N-Acetyl-muramyl-L-alanin Ligase) inhibiert. In spektrophotometischen Assays mit den E. coli-Enzymen MurA und MurC konnte ein Ki-Wert von 0.33 +/- 0.04 μM für das MurC Enzym und ein Ki-Wert von 3.4 +/- 1.1 μM für …
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A comparative study of in vitro chitin synthase activity in mucoraceous hosts of a mycoparasite
… the incorporation of the substrate [14C]-UDP-N-acetylglucosamine, into chitin. Most activity occurred in mixed membrane fraction. Inhibition of activity with Polyoxin D and activation with proteases, N-acetyl-glucosamine and magnesium and other ions was observed. Properties of the crude …
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Application of hydrogen deuterium exchange mass spectrometry in protein-ligand and protein-protein interactions
… The HDX-MS data revealed that the two substrates UDP-glucose (UDPG) and 3-phosphoglycerate (3PGA) can bind to MtGpgS independently, disagreeing with the previous proposal that 3PGA can only bind to MtGpgS after UDPG. Moreover, 3PGA was found to bind to or allosterically affect the UDPG binding …
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The Development of Substrates and Inhibitors of the PNAG Biosynthetic Machinery
… of PNAG biosynthesis in vitro. Analogues of UDP-GlcNAc incorporating NMR-active nuclei were synthesized using a chemoenzymatic approach and validated with the processive glycosyltransferase PgaCD. Additionally, substrate-based inhibitors of the deacetylase enzymes PgaB and SpPgda were …
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Structural Basis for Protein Recognition, Acyl-substrate Delivery, and Product Release by ACP in the Biosynthesis of Lipid A
… ACP recognition and nucleotide binding of UDP-GlcNAc. A comparison with the LpxD:ACP complexes uncovers that ACP utilizes different surface residues for recognition even amongst closely related acyltransferases, yet still relies on "electrostatic steering" for docking to its enzyme partner. …
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O antigen biosynthesis in Gram-negative bacteria: Characterization of alpha1,4-glucosyltransferase WclY from Escherichia coli O117 and development of glycosyltransferase inhibitors.
… is replaced by N-acetylglucosamine (GlcNAc) in the O antigen of E. coli O107 (GalNAc is N-acetylgalactosamine, Rha is Rhamnose, Gal is galactose). The glycosyltransferases that create the Glc/GlcNAcα1-4Gal linkage are WclY(O117) and WclY(O107), and differ in only 3 amino acid …
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Metabolic Pathways for Natural and Unnatural Sialic Acids
… sialic acid biosynthesis alters the levels of UDP-GlcNAc, a product of the hexosamine biosynthetic pathway. This results in changes in the branch structure of N-glycans and impairs galectin-1 binding to cells. Furthermore, I found that sialylation of N-glycans can further influence N-glycan …
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"Sugar Coat" Genetic & chemical validation of <i>Aspergillus fumigatus</i> cell wall targets
… polymer of β-(1,4) linked N-acetylglucosamine (GlcNAc), forms a rigid inner layer that is also partially hydrolysed during morphogenesis by glycoside hydrolase family 18 plant-type chitinases. In contrast, exploitation of glucosamine-6-phosphate N-acetyltransferase (GNA1) an enzyme in the highly …
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Mechanisms of polyphosphate degradation
The goal of my research has been to investigate the mechanisms by which inorganic polyphosphate (polyP) is degraded in vivo. PolyP is a linear chain of phosphate moieties linked through high-energy phosphoanhydride bonds and can range in size from three-phosphates-long to thousands. Naturally, …