Formylglycine generating enzyme (FGE) recognizes a pentapeptide consensus sequence, CxPxR, and it specifically oxidizes the cysteine in this sequence to an unusual aldehyde-bearing formylglyine. Nonetheless, the glycosylation on cell membranes remains not well characterized because of the lack of sensitive analytical methods. These functional groups can then undergo covalent reaction with exogenous agents bearing complementary functionality. The properties of therapeutic proteins can be enhanced by chemical modification. Exact mass measurements showed that S881 is highly unsaturated, tandem mass spectrometry indicated a polyisoprene-derived structure, and characterization of synthetic structural analogs confirmed that S881 is a previously undescribed sulfated derivative of dihydromenaquinone-9, the primary quinol electron carrier in M. tuberculosis. View details for Web of Science ID 000268395000075, View details for PubMedCentralID PMC2716393. The effort was enabled by a new high-fidelity pattern-searching and glycopeptide validation algorithm termed IsoStamp v2.0, as well as by novel stable isotope probes. The incorporation of noncanonical amino acids into recombinant proteins in Escherichia coli can be facilitated by the introduction of new aminoacyl-tRNA synthetase activity into the expression host. View details for Web of Science ID 000250487600015, View details for PubMedCentralID PMC2040404. MS of material collected on the tissue paper blots revealed 67 GalNAz-labeled proteins, including intracellular proteins. 364 Lomita Drive She followed similar lines of research during her postdoctoral studies, investigating therole of carbohydrates in inflammation. Applications to noninvasive imaging and glycoproteomic analyses are discussed. GPI-anchored proteins are structurally and functionally diverse and play vital roles in numerous biological processes. View details for Web of Science ID 000171801100023. 56Carolyn Bertozzi 12 Bertozzi won the prize for studying the sugar coats of cells. Protein glycosylation is widely recognized as a modulator of protein structure, localization, and cell-cell recognition in multicellular systems. Mucin-type O-glycans could be imaged as early as 7 hours postfertilization, during the gastrula stage of development. Glycans can be imaged by metabolic labeling with azidosugars followed by chemical reaction with imaging probes; however, tissue-specific labeling is difficult to achieve. 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. We labeled LAP fusion proteins expressed in living mammalian cells with Cy3, Alexa Fluor 568 and biotin. A., Cox, J. S. Noncovalent complexes of APS reductase from M-tuberculosis: Delineating a mechanistic model using ESI-FTICR MS. Gao, H., Leary, J., Carroll, K. S., Bertozzi, C. R., Chen, H. Self-assembled cellular microarrays patterned using DNA barcodes. A., Lo, A., Bertozzi, C. R. Metabolic labeling of glycans with azido sugars for visualization and glycoproteomics. This approach should be applicable to any glycosyltransferase or group-transfer enzyme that tolerates unnatural azido substrates. Carlson, B. L., Ballister, E. R., Skordalakes, E., King, D. S., Breidenbach, M. A., Gilmore, S. A., Berger, J. M., Bertozzi, C. R. A hydrophilic azacyclooctyne for Cu-free click chemistry, The glycosylphosphatidylinositol anchor: A complex membrane-anchoring structure for proteins, The Mycobacterium tuberculosis virulence factor trehalose dimycolate imparts desiccation resistance to model mycobacterial membranes. Mockl, L., Pedram, K., Roy, A., Krishnan, V., Gustavsson, A., Dorigo, O., Bertozzi, C., Moerner, W. Enzyme toolkit for selective enrichment and analysis of mucin-domain glycoproteins. Chidsey, C. E., Bertozzi, C. R., PUTVINSKI, T. M., Mujsce, A. M. Freeman Spogli Institute for International Studies, Institute for Computational and Mathematical Engineering (ICME), Institute for Human-Centered Artificial Intelligence (HAI), Institute for Stem Cell Biology and Regenerative Medicine, Stanford Institute for Economic Policy Research (SIEPR), Stanford Woods Institute for the Environment, Office of VP for University Human Resources, Office of Vice President for Business Affairs and Chief Financial Officer, Radiology - Rad/Molecular Imaging Program at Stanford, Maternal & Child Health Research Institute (MCHRI), aavelino@stanford.edu / gabbyg@stanford.edu, Directed Reading in Stem Cell Biology and Regenerative Medicine, Therapeutic Science at the Chemistry - Biology Interface, DOI 10.1146/annurev.biochem.71.110601.135334. One such glycolipid, Sulfolipid-1 (SL-1), consists of a trehalose-2-sulfate (T2S) core acylated with four lipid moieties. The Staudinger ligation takes advantage of the electrophilicity of the azide; however, the azide can also participate in cycloaddition reactions. Our data show that the cysteine residue reversibly reacts with the nitrile group on the CBT moiety to form an intermediate thioimidate, which undergoes irreversible SN transfer to the lysine residue, yielding an amidine-linked product. Genomic and proteomic profiling form a basis for biological discovery. Godula, K., Umbel, M. L., Rabuka, D., Botyanszki, Z., Bertozzi, C. R., Parthasarathy, R. Glycopeptide-preferring Polypeptide GalNAc Transferase 10 (ppGalNAc T10), Involved in Mucin-type O-Glycosylation, Has a Unique GalNAc-O-Ser/Thr-binding Site in Its Catalytic Domain Not Found in ppGalNAc T1 or T2. Experimental data confirmed that electronic perturbation of BARAC's aryl rings has a modest effect on reaction rate, whereas steric hindrance in the transition state can significantly retard the reaction. 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. Although the early steps in SL-1 biosynthesis are known, the machinery underlying the final acylation reactions is not understood. Carrico, I. S., Carlson, B. L., Bertozzi, C. R. A cell nanoinjector based on carbon nanotubes. Additionally, the isotopic signature imparted by the dibromide tag was detectable on a 12-kDa protein, suggesting applications in identifying large peptide fragments, such as those containing multiple or large posttranslational modifications (e.g., glycosylation). 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. Optimization of Metabolic Oligosaccharide Engineering with Ac4GalNAlk and Ac4GlcNAlk by an Engineered Pyrophosphorylase. This genetically encoded 'aldehyde tag' is no larger than a His(6) tag and can be exploited for numerous protein labeling applications. Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions. Comparison of the cDNA and genomic DNA sequences reveals that this transferase is encoded by 10 exons in a 10 kb region. The reaction features a large dynamic range of reactivity, showcasing second-order rate constants as high as 2.310(3) M(-1) s(-1) using diboron reaction partners. 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 000227308100055. View details for Web of Science ID 000321093800027. The galectin family of glycan-binding proteins is thought to mediate many cellular processes by oligomerizing cell surface glycoproteins and glycolipids into higher-order aggregates. Bowman, K. G., Cook, B. N., de Graffenried, C. L., Bertozzi, C. R. The evolving academic research environment, Chemical synthesis of lymphotactin: A glycosylated chemokine with a C-terminal mucin-like domain. The rapid assembly of a complex type N-linked glycopeptide mimetic was accomplished using this technique. Disruption of the cell architecture increased the number and the molecular weight distribution of azido-sialic acid tagged proteins. Importantly, glycopolymers containing biologically relevant branched oligosaccharides, such as sialyl Lewis(x), as well as sulfated glycosaminoglycan-like epitopes can be readily prepared using our methodology. The complex and diverse structures of GPI anchors suggest a rich spectrum of biological functions, but few have been confirmed experimentally because of the lack of appropriate techniques that allow for structural perturbation in a cellular context. Genome-scale knockout screens assigned putative functional relevance to the RNA-protein interactions observed by ChIRP-MS. K chhai 2022-ngin tet-to Nobel Fa-hok Ching . Mahal, L. K., Yarema, K. J., Bertozzi, C. R. An ELISA for selectins based on binding to a physiological ligand. StcEE447D is a pan-mucin stain derived from enterohemorrhagic Escherichia coli that is tolerant to a wide range of glycoforms. Here, we report a system for conditional activation of Golgi-resident sulfotransferases using a chemical inducer of dimerization. View details for DOI 10.1093/glycob/cwq037, View details for Web of Science ID 000278437800004, View details for PubMedCentralID PMC2900898. WebCarolyn Ruth Bertozzi (born October 10, 1966) is an American chemist. Woo, C. M., Felix, A., Zhang, L., Elias, J. E., Bertozzi, C. R. Inhibition of NGLY1 Inactivates the Transcription Factor Nrf1 and Potentiates Proteasome Inhibitor Cytotoxicity. Hsiao, S. C., Crow, A. K., Lam, W. A., Bertozzi, C. R., Fletcher, D. A., Francis, M. B. She completed her undergraduate degree in Chemistry from Harvard University in 1988 and her Ph.D. in Chemistry from UC Berkeley in 1993. Yang, A. C., Stevens, M. Y., Chen, M. B., Lee, D. P., Stahli, D., Gate, D., Contrepois, K., Chen, W., Iram, T., Zhang, L., Vest, R. T., Chaney, A., Lehallier, B., Olsson, N., du Bois, H., Hsieh, R., Cropper, H. C., Berdnik, D., Li, L., Wang, E. Y., Traber, G. M., Bertozzi, C. R., Luo, J., Snyder, M. P., Elias, J. E., Quake, S. R., James, M. L., Wyss-Coray, T. Membrane-tethered mucin-like polypeptides sterically inhibit binding and slow fusion kinetics of influenza A virus. Once released, HCBT and D-cysteine form firefly luciferin in situ, giving rise to a bioluminescent signal if and only if both chemical triggers proceed. Ngo, J. T., Adams, S. R., Deerinck, T. J., Boassa, D., Rodriguez-Rivera, F., Palida, S. F., Bertozzi, C. R., Ellisman, M. H., Tsien, R. Y. A predominantly hydrophobic aglycone site facilitates accommodation of a variety of 2-linked sialosides; a versatility that offers the potential for glycan hydrolysis across a range of biological and technological platforms. Sulfite is then released in a thioredoxin-dependent manner. View details for Web of Science ID 000174145500016. WebCarolyn Ruth Bertozzi is an American chemist and Nobel laureate, known for her wide-ranging work spanning both chemistry and biology. These results provide a guide for biologists in choosing a suitable ligation chemistry. The widespread role of sulfotransferases in modulating glycan function makes them prime targets for small-molecule modulators. The genome of Mycobacterium tuberculosis (Mtb) encodes nine putative sulfatases, none of which have a known function or substrate. This bacterial enzyme purified from Akkermansia muciniphila cleaves N-terminally to serine and threonine residues that are modified with (preferably asialylated) O-glycans. View details for DOI 10.1016/j.cell.2006.08.017, View details for Web of Science ID 000240675000013. ESI-FTICR MS was utilized to characterize a 4Fe-4S containing protein Mycobacterium tuberculosis APS reductase. View details for Web of Science ID 000240465200023, View details for PubMedCentralID PMC3233198. Bertozzi is a professor Thus, despite its inherent advantages in sample collection, OF is not widely used for population screening. Furthermore, we show that these mimetics enhance the survival of nonmalignant cells in a zebrafish model of metastasis. Here we show that a stf0-deletion mutant exhibits augmented survival in human but not murine macrophages, suggesting that SL-1 negatively regulates the intracellular growth of Mtb in a species-specific manner. We describe a chemical strategy directed toward identifying O-GlcNAc-modified proteins from living cells or proteins modified in vitro. To obtain structural information about these biomolecules, and the modifications they may undergo during different stages of cell growth and development, a mass spectrometry-based method was developed and used to obtain unambiguous structural information on the glycosaminoglycans (GAGs) that comprise heparin/HS. To address this shortcoming, we have developed a robust, high-throughput compatible, click chemistry-based approach to identify small molecules that interfere with the palmitoylation of Ras, a high value therapeutic target that is mutated in up to a third of human cancers. Disruption of stf0 in Mycobacterium smegmatis and M. tuberculosis resulted in the loss of T2S and SL-1 formation, respectively. Synthetic mimics of the complex assemblies found on cell surfaces can modulate cellular interactions and are under development as therapeutic agents. Sulfonucleotide reductases are a diverse family of enzymes that catalyze the first committed step of reductive sulfur assimilation. A major challenge in fundamental studies of galectin-ligand interactions is that their natural ligands comprise a heterogeneous collection of glycoconjugates that share related glycan structures but disparate underlying scaffolds. Investigators have developed tools including small molecule inhibitors, decoy substrates, and engineered proteins to modify cellular glycans. Disruption of cysH rendered Mtb auxotrophic for cysteine and methionine, and attenuated virulence in BALB/c and C57BL/6 immunocompetent mice. We used this technique to image fucosylated glycans in the enveloping layer of zebrafish embryos during the first 5 days of development. Increased the number and the molecular weight distribution of azido-sialic acid tagged proteins axis in fibroblasts at the invasive edge... T2S and SL-1 formation, respectively of enzymes that catalyze the first 5 days of development Drive She followed lines... 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