Hotsclaw, C. M., Sogi, K. M., Gilmore, S. A., Scheller, M. W., Leavell, M. D., Bertozzi, C. R., Leary, J. Kinetic analysis of the mutants identified residues that are essential for catalytic activity. Chemical inducers of dimerization (CIDs) are cell-permeable small molecules capable of dimerizing two protein targets. The sulfate assimilation pathway of Mtb produces a number of sulfur-containing metabolites with important contributions to pathogenesis and survival. To enable noninvasive, real-time, spatiotemporal quantitative imaging of fatty acid fluxes in animals, we created a bioactivatable molecular imaging probe based on long-chain fatty acids conjugated to a reporter molecule (luciferin). A. Sequential assembly of the septal cell envelope prior to V snapping in Corynebacterium glutamicum. Neutralization of acidic organelles directly with ammonium chloride or indirectly with bafilomycin A1 partially abrogated the growth restriction of these drugs. Although several previously described compounds bind to the unique acyl chain binding passage of LpxC with high affinity, strategies to target the enzyme's UDP-binding site have not been reported. Bertozzi, C. R., SINGER, M. S., ROSEN, S. D. L-selectin-carbohydrate interactions: Relevant modifications of the Lewis x trisaccharide. She is an elected member of the National Academy of Sciences, the American Academy of Arts and Sciences, and the German Academy of Sciences Leopoldina. Mycobacterium tuberculosis and Mycobacterium smegmatis possess three pathways for the synthesis of trehalose. View details for DOI 10.1371/journal.pgen.1008284. Binding was EDTA-sensitive and blocked by L-selectin-specific monoclonal antibodies. Grand Challenges in Chemistry for 2016 and Beyond. Both biochemical and structural data indicate the presence of an oxidized cysteine modification in the active site that may be relevant to catalysis. Generated in nine steps from a glucose analogue, DIMAC reacted with azide-labeled proteins and cells similarly to cyclooctynes. The approach provides a means for studying sulfate-dependent processes in cellular systems and, potentially, in vivo. These findings elucidate a mechanism of age-related microglial impairment and a strategy to restore homeostasis in the ageing brain. [27][28][29] This new field and technique allows researchers to chemically modify molecules in living organisms and not interrupt the processes of the cell. We report the discovery that boron nitride nanotubes (BNNTs), isosteres of CNTs with unique physical properties, are inherently noncytotoxic. View details for Web of Science ID 000172076800007, View details for PubMedCentralID PMC60788. Their removal by enzymatic means is shown to markedly enhance phagocytic efficiency. Cells bend their plasma membranes into highly curved forms to interact with the local environment, but how shape generation is regulated is not fully resolved. Some members of the family prefer previously gly co sylated peptides (ppGalNAc T7 and T10), whereas others are inhibited by neighboring gly co sy la tion (ppGalNAc T1 and T2). The active cuprous FGE complex was interrogated directly by X-ray absorption spectroscopy. We microinjected embryos with azidosugars at the one-cell stage, allowed the zebrafish to develop, and detected the metabolically labeled glycans with copper-free click chemistry. GRABOWSKI, J. J., Bertozzi, C. R., Jacobsen, J. R., Jain, A., Marzluff, E. M., Suh, A. Y. Bertozzi completed her undergraduate degree in Chemistry at Harvard University and her Ph.D. at UC Berkeley, focusing on the chemical synthesis of oligosaccharide analogs. View details for Web of Science ID 000392525600001, View details for PubMedCentralID PMC5255568. Here we present an ultrasensitive solution-phase method for detecting antibodies, termed antibody detection by agglutination-PCR (ADAP). View details for DOI 10.1016/j.bmc.2016.05.050, View details for Web of Science ID 000385905800005, View details for PubMedCentralID PMC5052108. This report describes our investigation into the extent of tolerance of the pathway toward additional structural alterations of the N-acyl substituent of ManNAc. However, its superior polarity and water solubility reduced nonspecific binding, thereby improving the sensitivity of azide detection. Bacterial sulfate assimilation pathways provide for activation of inorganic sulfur for the biosynthesis of cysteine and methionine, through either adenosine 5'-phosphosulfate (APS) or 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as intermediates. To use IsoTaG, cell culture samples are metabolically labeled with an azido- or alkynyl-sugar. View details for Web of Science ID 000384202600014, View details for PubMedCentralID PMC5023497, View details for DOI 10.1021/acscentsci.5b00386, View details for PubMedCentralID PMC4827657. Synthetic glycopolymers that emulate cell-surface mucins have been used to elucidate the role of mucin overexpression in cancer. View details for DOI 10.1074/jbc.M109.017236, View details for Web of Science ID 000268097400064, View details for PubMedCentralID PMC2740463. UDP-GlcNAc 2-epimerase and GlcNAc 2-epimerase are two enzymes capable of generating ManNAc from UDP-GlcNAc and GlcNAc, respectively. Using a recently described method (Mahal, L. K., Yarema, K. J., and Bertozzi, C. R. (1997) Science 276, 1125-1128), we delivered a uniquely reactive ketone group to endogenous cell surface sialic acid residues by treating cells with the ketone-bearing metabolic precursor N-levulinoylmannosamine (ManLev). Z. Multi-omics analysis of spatially distinct stromal cells reveals tumor-induced O-glycosylation of the CDK4-pRB axis in fibroblasts at the invasive tumor edge. Traditional spectrophotometric assays are not applicable to the NodST system since no shift in absorption accompanies sulfuryl group transfer. View details for DOI 10.1074/jbc.M809088200, View details for Web of Science ID 000265688300019, View details for PubMedCentralID PMC2676004. WebCarolyn Bertozzi, PhD. We previously synthesized a series of GPI anchor analogs with systematic deletions within the glycan core and coupled them to the GFP by a combination of expressed protein ligation and native chemical ligation [Paulick MG, Wise AR, Forstner MB, Groves JT, Bertozzi CR (2007) J Am Chem Soc 129:11543-11550]. Yang, A. C., Du Bois, H., Olsson, N., Gate, D., Lehallier, B., Berdnik, D., Brewer, K. D., Bertozzi, C. R., Elias, J. E., Wyss-Coray, T. IL-1R and MyD88 Contribute to the Absence of a Bacterial Microbiome on the Healthy Murine Cornea. View details for DOI 10.1021/jacs.6b03861, View details for PubMedCentralID PMC5327792, View details for DOI 10.1021/acscentsci.6b00224, View details for PubMedCentralID PMC4999963. Mutants with defects in sulfate assimilation indicate that the fate of sulfur in M. tb is a critical survival determinant for the bacteria during infection and suggest novel targets for tuberculosis drug therapy. This system enables the production of glycoproteins that are functionalized for specific chemical modifications at their glycosylation sites. Thus, we hypothesize that either MmpL8 transports molecules in addition to SL-1 that mediate host-pathogen interactions or the accumulation of SL(1278) in mmpL8 mutant cells interferes with other pathways required for growth during the early stages of infection. Tastan, O. Y., Debets, M. F., Malaker, S. A., Wisnovsky, S. P., Angelis, N., Wagner, L. S., Choi, J., Browne, W. M., Bineva-Todd, G., Cioce, A., Agbay, A. J., Li, Z., Briggs, D. C., Flynn, H., Roustan, C., Fernandez, D., Douglas, H. L., Kjaer, S., Snijders, A. P., Li, V. W., Bertozzi, C. R., Schumann, B. Beatty, K. E., Fisk, J. D., Smart, B. P., Lu, Y. Y., Szychowski, J., Hangauer, M. J., Baskin, J. M., Bertozzi, C. R., Tirrell, D. A. Bioluminescent Probes of Sulfatase Activity. With their native proteinaceous backbones and natural glycosidic linkages, these agonists are attractive for translational applications. View details for DOI 10.1038/nchembio0605-13, View details for Web of Science ID 000232621100006. Through a small molecule screen, we identified a cell-active NGLY1 inhibitor that disrupts the processing and function of Nrf1. The FGE recognition sequence, or aldehyde tag, can be inserted into heterologous recombinant proteins produced in either prokaryotic or eukaryotic expression systems. One such glycolipid, Sulfolipid-1 (SL-1), consists of a trehalose-2-sulfate (T2S) core acylated with four lipid moieties. Parak, W. J., Gerion, D., Zanchet, D., Woerz, A. S., Pellegrino, T., Micheel, C., Williams, S. C., Seitz, M., Bruehl, R. E., Bryant, Z., Bustamante, C., Bertozzi, C. R., Alivisatos, A. P. Stereloselective synthesis of myo-inositol via ring-closing metathesis: A building block for glycosylphosphatidylinositol (GPI) anchor synthesis. Furthermore, perturbation of MMCoA metabolism attenuated pathogen replication in mice. Sialylated glycans are found at elevated levels in many types of cancer and have been implicated in disease progression. Sulfite is then released in a thioredoxin-dependent manner. View details for Web of Science ID 000234391600034, View details for PubMedCentralID PMC2527029, View details for DOI 10.1002/ANIE.200502421, View details for Web of Science ID 000235246600005. Vocadlo, D. J., Hang, H. C., Kim, E. J., Hanover, J. Two approaches that emphasize developing selective methods to dissect, modify, and control receptor-ligand interactions at the cellular interface are discussed. Malaker, S. A., Shon, J., Pedram, K., Riley, N. M., Bertozzi, C. R. AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. An RNA-centric dissection of host complexes controlling flavivirus infection. Highlights of recent progress include an extension of the list of instances of selectin participation in inflammatory diseases, further definition of selectin carbohydrate specificities, and identification of their carbohydrate-based ligands. We report here a study of mycomembrane dynamics that was enabled by trehalose-fluorophore conjugates capable of labeling trehalose glycolipids in live actinomycetes. In the first step of the pathway, APS reductase catalyzes the reduction of adenosine 5'-phosphosulfate (APS) to adenosine 5'-phosphate (AMP) and sulfite with reducing equivalents from the protein cofactor, thioredoxin. In the past decade advances in genomics, proteomics and mass spectrometry have enabled the association of specific glycan structures with disease states. Quantifying and controlling the orientation of surface-bound macromolecules is crucial to a wide range of processes in areas as diverse as biology, materials science, and nanotechnology. Data from two independent probes, fluorophores conjugated directly to the polymer backbone and fluorescent proteins bound to the sugar groups, unexpectedly show that the mucin mimic molecules lie flat along the membrane. View details for Web of Science ID 000279196500017, View details for PubMedCentralID PMC2890245. The ability to access glycopeptides of this type through chemical synthesis will facilitate further mechanistic studies. 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