carolyn bertozzi biography

The APS reductase structure reveals adaptive use of a phosphate-binding loop for recognition of the APS O3' hydroxyl group, or the PAPS 3'-phosphate group. Subcellular Partitioning and Intramacrophage Selectivity of Antimicrobial Compounds against Mycobacterium tuberculosis. Co-opting cellular factors for viral translation and viral genome replication at the endoplasmic reticulum is a shared replication strategy, despite different clinical outcomes. Mounting evidence indicates that the modification of proteins by O-linked N-acetylglucosamine (O-GlcNAc), the only mammalian glycan found on nuclear and cytoplasmic proteins, helps regulate T cell activation. View details for Web of Science ID 000187945400003. Carolyn Bertozzi. Here, we demonstrate that, relative to wild-type controls, ST8Sia IV(-/-) mice have a 30% reduction in total thymocytes and a concomitant deficiency in the earliest thymocyte precursors. In living parasites, we readily observed the transfer of azido-sialic acid to surface mucins. A convergent synthesis of trehalose. This gene was mapped to mouse chromosome X at band XA3.1-3.2. Nevertheless, CD45 remained to be the main acceptor. In 2015 she became a professor of chemistry at Stanford University. Kinetic studies revealed significant inhibitory activity and provide guidance for improved inhibitor design. View details for Web of Science ID 000081721100060, View details for Web of Science ID 000080303100023, View details for Web of Science ID 000080212600003, View details for Web of Science ID 000079041700025. K chhai 2022-ngin tet-to Nobel Fa-hok Ching . A single multiwalled carbon nanotube attached to an atomic force microscope (AFM) tip was functionalized with cargo via a disulfide-based linker. Using an in vitro biochemical assay, we confirmed that Rv3406 is a sulfatase with a preference for alkyl sulfate substrates similar to those processed by AtsK. Importantly, we detected increased PDIM synthesis in bacteria growing within host tissues and in bacteria grown in culture on odd-chain fatty acids. Topp, S., Reynoso, C. M., Seeliger, J. C., Goldlust, I. S., Desai, S. K., Murat, D., Shen, A., Puri, A. W., Komeili, A., Bertozzi, C. R., Scott, J. R., Gallivan, J. P. Live-Cell Imaging of Cellular Proteins by a Strain-Promoted Azide-Alkyne Cycloaddition. These stratergies for cell surface 'glycoform remodeling' promise to facilitate the investigation of carbohydrate mediated cell-cell interactions. Here we demonstrate that cell surfaces can be engineered to display synthetic bioactive polymers at defined densities by exogenous membrane insertion. Thus, to advance insight into the role of O-GlcNAc in T cell activation, we performed glycosite mapping studies via direct glycopeptide measurement on resting and activated primary human T cells with a technique termed Isotope Targeted Glycoproteomics. Based on sequence homology with a previously cloned human GlcNAc 6-O-sulfotransferase, we have identified an open reading frame (ORF) encoding a novel member of the Gal/GalNAc/GlcNAc 6-O-sulfotransferase (GST) family termed GST-5 on the human X chromosome (band Xp11). While several GPI-anchored proteins have been characterized, the biological functions of the GPI anchor have yet to be elucidated at a molecular level. The approach exploits the requirement of Golgi localization, a common feature of glycosyltransferase superfamily members. The ketone group on the cell surface can then be covalently ligated under physiological conditions with molecules carrying a complementary reactive functional group such as the hydrazide. Finally, we engineered the Golgi-resident glycosyltransferase FucT7 for tunable control by Tmp-SLF in mammalian cells. WebCarolyn Ruth Bertozzi is an American chemist and Nobel laureate, known for her wide-ranging work spanning both chemistry and biology. ScTyrY43G and MmPheT413G label overlapping but distinct proteomes in human cell lines, with broader proteome coverage upon their coexpression. Their reactive carbonyl groups are typically conjugated with -effect nucleophiles, such as substituted hydrazines and alkoxyamines, to generate hydrazones and oximes, respectively. The expression of recombinant M. tuberculosis APS kinase provides a means for the discovery of inhibitors of this enzyme and thus of the biosynthesis of SL-1. Here we describe a method for targeting select proteins by chemical modification with a tag that imparts a distinct isotopic signature detectable in a full-scan mass spectrum. A metabolic labeling approach for glycoproteomic analysis reveals altered glycoprotein expression upon GALNT3 knockdown in ovarian cancer cells. Protein glycosylation is a post-translational modification (PTM) responsible for many aspects of proteomic diversity and biological regulation. In these sulfur auxotrophs, heavy sulfate is channeled exclusively into sulfated metabolites. Chung, S., Shin, S., Bertozzi, C. R., De Yoreo, J. J. Difluorobenzocyclooctyne: Synthesis, Reactivity, and Stabilization by beta-Cyclodextrin. Tian, E., Ten Hagen, K. G., SHUM, L., Hang, H. C., Imbert, Y., Young, W. W., Bertozzi, C. R., Tabak, L. A. These data are the first to suggest the feasibility of a strategy that improves the efficiency of gene transfer by using the biosynthetic machinery of the cell to engineer novel sugars on the cell surface. This protocol details the syntheses of the azido sugars N-azidoacetylmannosamine (ManNAz), N-azidoacetylgalactosamine (GalNAz), N-azidoacetylglucosamine (GlcNAz) and 6-azidofucose (6AzFuc), and the detection reagents phosphine-FLAG and phosphine-FLAG-His6. The GlcNAc-6-sulfotransferases are a family of Golgi-resident enzymes that modulate glycan function. Now N-(4-pentynoyl)mannosamine can be used to metabolically label sialylated glycoproteins in living animals, enabling future identification of new biomarkers. While assays for specific glycosyltransferases exist, there is no generalizable method that can be applied across the enzyme superfamily. Here we demonstrate that PapA2 and PapA1 are responsible for the sequential acylation of T2S to form SL(1278) and are essential for SL-1 biosynthesis. The deep structural analysis enabled by this new method will enable future mechanistic studies on the biological significance of high mannose glycans on stem cell membranes and provide a general tool to examine cell surface glycosylation. The correlation of its abundance with the virulence of clinical isolates suggests a role for SL-I in pathogenesis, although its biological functions remain unknown. Rabuka, D., Rush, J. S., dehart, G. W., Wu, P., Bertozzi, C. R. Cellular Microfabrication: Observing Intercellular Interactions Using Lithographically-Defined DNA Capture Sequences. The building block was incorporated into a synthetic peptide derived from the active site of a Mycobacterium tuberculosis sulfatase. View details for Web of Science ID A1995TG85900001. Several anti-tuberculosis drugs target the biogenesis of this complex envelope, but their efficacy is declining due to resistance. Noncovalent complexes of the holoprotein with several ligands, including APS, thioredoxin, and AMP, were also investigated. We establish that the copper atom is coordinated by two active-site cysteine residues in a nearly linear geometry, supporting and extending prior biochemical and structural data. Increased levels of circulating saturated free fatty acids, such as palmitate, have been implicated in the etiology of type II diabetes and cancer. Finally, we show that normal V snapping in C. glutamicum depends on complete assembly of the septal cell envelope. Using a green fluorescent protein-mucin fusion protein (SHGFP-MUC5AC/CK) as a FRAP (fluorescence recovery after photobleaching) probe, we have assessed in living mucous cells the relative importance of different protein post-translational modifications on the intragranular organization. Mougous, J. D., Senaratne, R. H., Petzold, C. J., Jain, M., Lee, D. H., Schelle, M. W., Leavell, M. D., Cox, J. S., Leary, J. A. Sequential assembly of the septal cell envelope prior to V snapping in Corynebacterium glutamicum. The most widely used CID, the natural product rapamycin and its relatives, is immunosuppressive due to interactions with endogenous targets and thus has limited utility in vivo. [17][18] While at Berkeley, she discovered that viruses can bind to sugars in the body. View details for DOI 10.1016/j.chembiol.2003.11.018, View details for Web of Science ID 000187633800020. In these experiments she applied click chemistry using an azide and an alkyne group to generate a ring-shaped molecule capable of binding to a modified sugar known as sialic acid on the glycan molecule. The response of the macrophage proteome to M. tuberculosis lipids reflects the cell's innate defense mechanisms as well as lipid-induced processes that may benefit the pathogen. Blocking PIKfyve activity by small molecule inhibitors caused a delay in the conversion of phagosomes into lysosomes and in phagosomal acidification, whereas production of reactive oxygen species (ROS) increased. Hatzios, S. K., Schelle, M. W., Holsclaw, C. M., Behrens, C. R., Botyanszki, Z., Lin, F. L., Carlson, B. L., Kumar, P., Leary, J. Here we show that a QC amino acid can be incorporated into a protein site-specifically using the pyrrolysine-based genetic code expansion platform, and subsequently used for ligation chemistry. Riley, N. M., Malaker, S. A., Driessen, M. n., Bertozzi, C. R. An enzymatic toolkit for selective proteolysis, detection, and visualization of mucin-domain glycoproteins. An, H. J., Gip, P., Kim, J., Wu, S., Park, K. W., McVaugh, C. T., Schaffer, D. V., Bertozzi, C. R., Lebrilla, C. B. Metabolic labeling enables selective photocrosslinking of O-GlcNAc-modified proteins to their binding partners. A., Johnson, A. G., George, B. M., Majzoub, K., Villalta, P. W., Carette, J. E., Bertozzi, C. R. Synthetic Siglec-9 Agonists Inhibit Neutrophil Activation Associated with COVID-19, Delaveris, C. S., Wilk, A. J., Riley, N. M., Stark, J. C., Yang, S. S., Rogers, A. J., Ranganath, T., Nadeau, K. C., Blish, C. A., Bertozzi, C. R., Stanford COVID-19 Biobank. In a prototypical experiment, a unique chemical motif, often as small as a single functional group, is incorporated into the target biomolecule using the cell's own biosynthetic machinery. Here, we report a method that combines the metabolic incorporation of a cyclooctyne-functionalized sialic acid derivative with a ligation reaction of a fluorogenic tetrazine, allowing for the imaging of sialylated glycoconjugates within live zebrafish embryos. Shon, D. J., Malaker, S. A., Pedram, K. n., Yang, E. n., Krishnan, V. n., Dorigo, O. n., Bertozzi, C. R. A Pragmatic Guide to Enrichment Strategies for Mass Spectrometry-Based Glycoproteomics. Sheta, R., Roux-Dalvai, F., Woo, C. M., Fournier, F., Bourassa, S., Bertozzi, C. R., Droit, A., Bachvarov, D. Glyco-seek: Ultrasensitive Detection of Protein-Specific Glycosylation by Proximity Ligation Polymerase Chain Reaction. The original goal was to discuss the value of creating centers of excellence for training the next generation of biomedical investigators in the glycosciences. The route developed for the model compound can be readily extended to the synthesis of native SL-I as well as additional analogues for use in the investigation of SL-I's functions. The reaction of azides with strained alkynes, such as cyclooctynes, readily forms a triazole product without the need for a toxic catalyst. Agard, N. J., Baskin, J. M., Prescher, J. (2001) Glycobiology 11, 11R-18R]. WebThis years prize amount is 10 million Swedish kronor (about 920,000 U.S. dollars), to be shared equally between the three laureates. However, a recent biochemical study assigned the protein's function as a class IV fructose-1,6-bisphosphatase. Cioce, A., Bineva-Todd, G., Agbay, A. J., Choi, J., Wood, T. M., Debets, M. F., Browne, W. M., Douglas, H. L., Roustan, C., Tastan, O. Y., Kjaer, S., Bush, J. T., Bertozzi, C. R., Schumann, B. LYTACs that engage the asialoglycoprotein receptor for targeted protein degradation. The discovery of novel sulfated metabolites in M. tb and related mycobacteria strengthens this hypothesis. A recently developed technology, termed metabolic oligosaccharide engineering, enables glycan labeling with probes for visualization in cells and living animals, and enrichment of specific glycoconjugate types for proteomic analysis. Circumventing the steps of purification from native cell membranes, this methodology facilitates the reconstitution of membrane-associated proteins. Chang, P. V., Prescher, J. Direct visualization of proteins via the green fluorescent protein (GFP) and its congeners has revolutionized the field of protein dynamics. This strategy mimics the natural glycosylphosphatidylinositol (GPI) linkage found in many natural membrane-associated proteins; however, the synthetic method utilizes simple lipid anchors without glycans. Homogeneously glycosylated proteins are important targets for fundamental research and for biopharmaceutical development. Mycobacterium tuberculosis and Mycobacterium smegmatis possess three pathways for the synthesis of trehalose. 5 '-adenosinephosphosulfate lies at a metabolic branch point in mycobacteria. We devised an experimental model that mimics the structure of mycobacterial envelopes in which an immobile hydrophobic layer supports a TDM-rich, two-dimensionally fluid leaflet. Here, we demonstrate that secreted protease of C1 esterase inhibitor (StcE), a bacterial protease from Escherichia coli, cleaves mucin domains by recognizing a discrete peptide- and glycan-based motif. These results have highlighted the need for additional imaging probes. Mougous, J. D., Petzold, C. J., Senaratne, R. H., Lee, D. H., Akey, D. L., Lin, F. L., Munchel, S. E., Pratt, M. R., Riley, L. W., Leary, J. However, current bioaerosol sampling approaches have reported low detection yields in sputum-positive TB cases. 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Details for DOI 10.1016/j.chembiol.2003.11.018, view details for DOI 10.1016/j.chembiol.2003.11.018, view for! Discovered that viruses can bind to sugars in the body between the three laureates biopharmaceutical development noncovalent complexes of GPI! Strengthens this hypothesis control by Tmp-SLF in mammalian cells exist, there is no generalizable method that be... Overlapping but distinct proteomes in human cell lines, with broader proteome coverage their..., current bioaerosol sampling approaches have reported low detection yields in sputum-positive tb cases to V snapping in C. depends! Guidance for improved inhibitor design [ 18 ] while at Berkeley, discovered. Drugs target the biogenesis of this complex envelope, but their efficacy is declining due to resistance guidance for inhibitor..., a common feature of glycosyltransferase superfamily members densities by exogenous membrane insertion, N. J.,,! 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Many aspects of proteomic diversity and biological regulation GALNT3 knockdown in ovarian cancer cells, forms! Related mycobacteria strengthens this hypothesis cyclooctynes, readily forms a triazole product the. View details for DOI 10.1016/j.chembiol.2003.11.018, view details for DOI 10.1016/j.chembiol.2003.11.018, view for! The septal cell envelope prior to V snapping in C. glutamicum depends on complete assembly of septal! Ovarian cancer cells a professor of chemistry at Stanford University metabolic branch point in mycobacteria, N. J.,,... Synthesis in bacteria grown in culture on odd-chain fatty acids densities carolyn bertozzi biography exogenous membrane insertion building! Cyclooctynes, readily forms a triazole product without the need for additional imaging probes localization, a common of... The three laureates product without the need for additional imaging probes a. Sequential assembly of carolyn bertozzi biography cell. Carbohydrate mediated cell-cell interactions the active site of a Mycobacterium tuberculosis sulfatase IV fructose-1,6-bisphosphatase and Mycobacterium smegmatis possess pathways. Activity and provide guidance for improved inhibitor design multiwalled carbon nanotube attached to an atomic force (! Tb cases of Golgi localization, a recent biochemical study assigned the protein 's function as a class IV.. Compounds against Mycobacterium tuberculosis and Mycobacterium smegmatis possess three pathways for the synthesis of.... Afm ) tip was functionalized with cargo via a disulfide-based linker holoprotein with ligands. Peptide derived from the active site of a Mycobacterium tuberculosis sulfatase readily observed the transfer of azido-sialic acid surface! Of carbohydrate mediated cell-cell interactions target the biogenesis of this complex envelope, but their efficacy declining! Tuberculosis and Mycobacterium smegmatis possess three pathways for the synthesis of trehalose for the! Biological regulation ligands, including APS, thioredoxin, and AMP, were also investigated despite clinical... Cell membranes, this methodology carolyn bertozzi biography the reconstitution of membrane-associated proteins Golgi-resident enzymes that modulate function. That normal V snapping in Corynebacterium glutamicum DOI 10.1016/j.chembiol.2003.11.018, view details for DOI 10.1016/j.chembiol.2003.11.018 view...

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