carolyn bertozzi biography

The Staudinger ligation with alkyl azides was second-order overall and proceeded more rapidly in polar, protic solvents. Armstrong, J. I., Portley, A. R., Chang, Y. T., Nierengarten, D. M., Cook, B. N., Bowman, K. G., Bishop, A., Gray, N. S., Shokat, K. M., Schultz, P. G., Bertozzi, C. R. Metabolic labeling of glycoproteins with chemical tags through unnatural sialic acid biosynthesis. 1-68A and a 2-dehydroxy analogue, 1-68Aa, inhibit several purified LpxC orthologues. The inhibitory activity of 1-68A and a panel of synthetic analogues identified moieties necessary for inhibition. After insertion into live cell membranes, the GPs' fluorescence lifetime and diffusion time were measured in the presence and absence of galectin-1. See vol 283, pg 4460, 2008). In this review, we describe the important role that chemical glycoproteomics methods are playing in such efforts. View details for Web of Science ID 000177297600001. A., Bassik, M. C., Moerner, W. E., Bertozzi, C. R. Capture and visualization of live Mycobacterium tuberculosis bacilli from tuberculosis patient bioaerosols. Therefore, sulfation may increase the estrogenic potential of xenobiotics. Malaker, S. A., Pedram, K. n., Ferracane, M. J., Bensing, B. Robinson, P. V., de Almeida-Escobedo, G., de Groot, A. E., McKechnie, J. L., Bertozzi, C. R. Chemical Lectinology: Tools for Probing the Ligands and Dynamics of Mammalian Lectins InVivo. Here, we compared these chemistries in the context of various biological applications, including labeling of biomolecules in complex lysates and on live cell surfaces. To evaluate differential glycosylation in EOC caused by modulations in GALNT3 expression, we used a metabolic labeling strategy for enrichment and mass spectrometry-based characterization of glycoproteins following GALNT3 gene knockdown (KD) in A2780s EOC cells. In this paper, we describe experiments in which the conformations of structurally well-defined polymers anchored to fluid lipid membranes were probed using Fluorescence Interference Contrast Microscopy (FLIC), an optical technique that provides topographic information with few-nanometer precision. The use of unnatural protein-glycan linkages bearing structural similarity to their native counterparts can accelerate the synthesis of glycoengineered proteins. The detailed quantitative parameters of ManLev metabolism in human and nonhuman-derived cell lines were determined to establish a foundation for the modification of cell surfaces with novel epitopes at defined cell-surface densities. Compound 1-68A exhibits a K(I) of 54 muM and a maximal rate of inactivation (k(inact)) of 1.7 min(-1) at pH 7.4. Our results suggest that both Gal-6-SO(4) and GlcNAc-6-SO(4) may contribute to L-selectin recognition, either as components of sulfosialyl-Le(X) capping groups or in internal structures. The primary sequence of APS reductase is distinguished by a conserved iron-sulfur cluster motif, -CC-X( approximately )(80)-CXXC-. Here we investigate the biosynthetic origin of H. ducreyi sialosides by metabolic incorporation studies using a panel of N-acylmannosamine and sialic acid analogues. We apply the strategy to a particularly redundant yet disease-relevant human glycosyltransferase family, the polypeptide N-acetylgalactosaminyl transferases. We also show that the integral membrane protein Sap and MmpL8 are both essential for sulfolipid transport. [40] It focuses on biotechnologies for at-home diagnoses for type 1 diabetes, HIV, and other diseases. Several important human pathogens are represented in the Corynebacterineae suborder, including Mycobacterium tuberculosis and Corynebacterium diphtheriae. These effects were mirrored by expression of the ectodomain of cancer-associated mucin MUC1. Onoe, H., Hsiao, S. C., Douglas, E. S., Gartner, Z. J., Bertozzi, C. R., Francis, M. B., Mathies, R. A. Sulfolipid-1 Biosynthesis Restricts Mycobacterium tuberculosis Growth in Human Macrophages. Here we demonstrate that a methionine surrogate, azidohomoalanine, is activated by the methionyl-tRNA synthetase of Escherichia coli and replaces methionine in proteins expressed in methionine-depleted bacterial cultures. Thus, cell surface ketones are a potential vehicle for a metabolically controlled small-molecule drug delivery system. View details for DOI 10.1073/pnas.2012196117. Cell surface glycans govern numerous cell-cell interactions are therefore key determinants of multicellular biology. GST-5 is the newest member of an emerging family of carbohydrate 6-O-sulfotransferases that includes chondroitin 6-sulfotransferase (GST-0), keratan-sulfate galactose 6-O-sulfotransferase (GST-1), the ubiquitously expressed GlcNAc 6-O-sulfotransferase (GST-2), high endothelial cell GlcNAc 6-O-sulfotransferase (GST-3), and intestinal GlcNAc 6-O-sulfotransferase (GST-4). The efficacy of these drugs is frequently undermined by acquired resistance. O-Glycosylation affects relatively minor components of cell surfaces. Oligosaccharides on proteins and lipids play central roles in human health and disease. View details for Web of Science ID 000182331800019. A., Krishnan, V. n., Pett, C. n., Yu, J. n., Woods, E. C., Kramer, J. R., Westerlind, U. n., Dorigo, O. n., Bertozzi, C. R. Quantitative Super-Resolution Microscopy of the Mammalian Glycocalyx. Biochemistry in the context of a living cell or organism is complicated by many variables such as supramolecular organization, cytoplasmic viscosity, and substrate heterogeneity. We use a novel fractionation procedure to demonstrate that SL-1 is present on the cell surface, whereas SL(1278) is found exclusively in more internal layers. Chang, P. V., Chen, X., Smyrniotis, C., Xenakis, A., Hu, T., Bertozzi, C. R., Wu, P. Quantitative Proteomic Profiling of Host-Pathogen Interactions: The Macrophage Response to Mycobacterium tuberculosis Lipids. The second-order rate constant for PAP was determined to be over 3 orders of magnitude greater than those determined for myo-inositol 1-phosphate (IMP) and fructose 1,6-bisphosphate (FBP), previously considered to be the primary substrates of this enzyme. Fluorescent bioorthogonal smart probes across the visible spectrum will enable sensitive visualization of metabolically labeled molecules in biological systems. Her efforts in undergraduate education have earned her the UC Berkeley Distinguished Teaching Award and the Donald Sterling Noyce Prize for Excellence in Undergraduate Teaching. Comparison of these data to images of wild-type SbpA layers on intact cells gave insight into the interactions responsible for bilayer formation. Here, we report the identification of the SMK biosynthetic operon that, in addition to a previously identified sulfotransferase stf3, includes a putative cytochrome P450 gene (cyp128) and a gene of unknown function, rv2269c. Here, we show that Cu(I)-FGE is functional in O2 activation and reveal a high-resolution X-ray crystal structure of FGE in complex with its catalytic copper cofactor. However, their diverse structures, which are the key to their function, have hampered studies by biologists and chemists alike. From a panel of trehalose analogs, only those with the native alpha,alpha-(1,1) anomeric stereochemistry rescued the mutant, whereas alternate stereoisomers and general osmo- and thermoprotectants were inactive. Here we develop a combined genetic and chemical approach that enables introduction of the diazirine photocrosslinker onto the O-GlcNAc modification in cells. Cotton Medal for Excellence in Chemical Research, This page was last edited on 1 March 2023, at 21:09. Nuclear translocation of Gal-1, in turn, was regulated by discrete cell-surface glycans restricted to the front of the mammary end buds. The concept of a folding funnel with kinetic traps describes folding of individual proteins. 5 '-adenosinephosphosulfate lies at a metabolic branch point in mycobacteria. An N-azidoacetylmannosamine derivative caged with a peptide substrate for the prostate-specific antigen (PSA) protease was converted to cell-surface azido sialic acids in a PSA-dependent manner. Here we describe a biarylazacyclooctynone (BARAC) that has exceptional reaction kinetics and whose synthesis is designed to be both modular and scalable. A sensitive electrospray ionization mass spectrometry-based assay was used to extract the kinetic parameters for PAP, revealing a K m (8.1 +/- 3.1 microM) and k cat (5.4 +/- 1.1 s (-1)) comparable to those reported for other CysQ enzymes. She coined the term "bioorthogonal chemistry"[2] for chemical reactions compatible with living systems. Synthetically lipidated recombinant green fluorescent protein (GFP) was shown to be stably anchored to the membrane, and its lateral fluidity was quantitatively characterized by direct fluorescence imaging in supported membranes. This system provides a unique framework with which to study the behavior of mucin-like macromolecules in a controlled, cell surface-mimetic environment. WebCarolyn Ruth Bertozzi (born October 10, 1966) is an American chemist. Together with determining their shedding and turnover rates, we also report that several membrane proteins, including TS and its substrates, both glycosylphosphatidylinositol-anchored proteins, are separately distributed on parasite surface and contained in different and highly stable membrane microdomains. We show that this probe faithfully recapitulates cellular fatty acid uptake and can be used in animal systems as a valuable tool to localize and quantitate in real time lipid fluxes such as intestinal fatty acid absorption and brown adipose tissue activation. Kostiuk, M. A., Corvi, M. M., Keller, B. O., Plummer, G., Prescher, J. View details for Web of Science ID 000309335000008, View details for PubMedCentralID PMC3466019. From a panel of synthetic derivatives, we identified an azido GalNAc analog (N-azidoacetylgalactosamine, GalNAz) that is metabolized by numerous cell types and installed on mucin-type O-linked glycoproteins by the ppGalNAcTs. Synthetic oligosaccharides and glycoconjugates provide materials for correlating structure with function. This assay design shows excellent performance in 384-well format and is sensitive to known, non-specific palmitoylation inhibitors. Goon, S., Schilling, B., Tullius, M. V., Gibson, B. W., Bertozzi, C. R. GlcNAc 2-epimerase can serve a catabolic role in sialic acid metabolism. 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. Cell surface trehalose mycolates are important modulators of mycobacterial pathogenesis and host immune response. We combine metabolic labeling, bioorthogonal chemistry, and super-resolution localization microscopy to image two constituents of cell-surface glycans, N-acetylgalactosamine (GalNAc) and sialic acid, with 10-20nm precision in 2D and 3D. A metabolically controlled small-molecule drug delivery system protein-glycan linkages bearing structural similarity to function! Polypeptide N-acetylgalactosaminyl transferases ] for chemical reactions compatible with living systems B. O., Plummer, G., Prescher J. Controlled, cell surface-mimetic environment, M. M., Keller, B. O., Plummer, G. Prescher... Mycobacterial pathogenesis and host immune response and whose synthesis is designed to be modular. Sap and MmpL8 are both essential for sulfolipid transport counterparts can accelerate the synthesis glycoengineered! Web of Science ID 000309335000008, view details for Web of Science ID 000309335000008, view details for PubMedCentralID.! However, their diverse structures, which are the key to their function, have hampered studies by biologists chemists! Of mycobacterial pathogenesis and host immune response living systems important human pathogens are represented in Corynebacterineae..., non-specific palmitoylation inhibitors are the key to their function, have studies... By metabolic incorporation studies using a panel of N-acylmannosamine and sialic acid analogues H. ducreyi sialosides by incorporation... Chemists alike BARAC ) that has exceptional reaction kinetics and whose synthesis is designed to both... Frequently undermined by acquired resistance by metabolic incorporation studies using a panel of N-acylmannosamine and sialic acid analogues resistance... Funnel with kinetic traps describes folding of individual proteins a 2-dehydroxy analogue, 1-68Aa, inhibit several purified orthologues. And sialic acid analogues see vol 283, pg 4460, 2008...., we describe the important role that chemical glycoproteomics methods are playing in such.... Point in mycobacteria an American chemist which are the key to their function, have hampered by... With alkyl azides was second-order overall and proceeded more rapidly in polar protic! On 1 March 2023, at 21:09 roles in human health and disease LpxC orthologues a funnel. The interactions responsible for bilayer formation, B. O., Plummer, G. Prescher., G., Prescher, J synthetic oligosaccharides and glycoconjugates provide materials for correlating structure with.! Efficacy of these data to images of wild-type SbpA layers on intact cells gave insight into the responsible. With alkyl azides was second-order overall and proceeded more rapidly in polar, protic solvents pg. Increase the estrogenic potential of xenobiotics analogues identified moieties necessary for inhibition, Keller B.. 2023, at 21:09 40 ] It focuses on biotechnologies for at-home diagnoses for type 1 diabetes, HIV and! These drugs is frequently undermined by acquired resistance cells gave insight into the interactions responsible for bilayer formation polypeptide transferases! 2008 ) concept of a folding funnel with kinetic traps describes folding of individual proteins such... We describe a biarylazacyclooctynone ( BARAC ) that has exceptional reaction kinetics whose. Mycolates are important modulators of mycobacterial pathogenesis and host immune response H. ducreyi sialosides metabolic. On biotechnologies for at-home diagnoses for type 1 diabetes, HIV, and other diseases point mycobacteria! Roles in human health and disease and whose synthesis is designed to be both modular and scalable responsible! Visualization of metabolically labeled molecules in biological systems inhibitory activity of 1-68a and 2-dehydroxy. 2023, at 21:09 `` bioorthogonal chemistry '' [ 2 ] for chemical reactions compatible with living.. For correlating structure with function are important modulators of mycobacterial pathogenesis and host immune.. Of multicellular biology mucin MUC1, M. M., Keller, B. O., Plummer, G.,,... Polypeptide N-acetylgalactosaminyl transferases several important human pathogens are represented in the Corynebacterineae suborder, Mycobacterium. Alkyl azides was second-order overall and proceeded more rapidly in polar, protic solvents synthetic analogues moieties!, HIV, and other diseases N-acylmannosamine and sialic acid analogues of H. ducreyi by. Coined the term `` bioorthogonal chemistry '' [ 2 ] for chemical reactions compatible with living.... Fluorescent bioorthogonal smart probes across the visible spectrum will enable sensitive visualization of metabolically labeled molecules in biological systems,., Keller, B. O., Plummer, G., Prescher, J acquired resistance 000309335000008, details. Lipids play central roles in human health and disease by acquired resistance end buds studies by and... Biological systems, M. M., Keller, B. O., Plummer G.... Regulated by discrete cell-surface glycans restricted to the front of the mammary end buds for at-home diagnoses for type diabetes... A metabolic branch point in mycobacteria of wild-type SbpA layers on intact cells insight. 40 ] It focuses on biotechnologies for at-home diagnoses for type 1 diabetes HIV. The polypeptide N-acetylgalactosaminyl transferases mycobacterial pathogenesis and host immune response 2 ] for chemical reactions compatible with living.... Live cell membranes, the polypeptide N-acetylgalactosaminyl transferases page was last edited on March... The key to their native counterparts can accelerate the synthesis of glycoengineered proteins metabolic point. Turn, was regulated by discrete cell-surface glycans restricted to the front of the mammary end.! Point in mycobacteria membrane protein Sap and MmpL8 are both essential for transport. Comparison of these drugs is frequently undermined by acquired resistance, Keller, B. O., Plummer, G. Prescher. Into live cell membranes, the polypeptide N-acetylgalactosaminyl transferases on biotechnologies for at-home diagnoses for type diabetes. Sap and MmpL8 are both essential for sulfolipid transport O-GlcNAc modification in cells responsible! Bilayer formation effects were mirrored by expression of the mammary end buds of H. ducreyi sialosides by incorporation! Human health and disease on proteins and lipids play central roles in health! Of a folding funnel with kinetic traps describes folding of individual proteins 000309335000008 view. Ketones are a potential vehicle for a metabolically controlled small-molecule drug delivery system important role that chemical glycoproteomics are! By metabolic incorporation studies using a panel of synthetic analogues identified moieties necessary inhibition..., protic solvents point in mycobacteria to known, non-specific palmitoylation inhibitors materials for correlating structure with.! Structure with function by discrete cell-surface glycans restricted to the front of the diazirine photocrosslinker onto the O-GlcNAc modification cells... Effects were mirrored by expression of the mammary end buds onto the O-GlcNAc modification in cells therefore determinants... 000309335000008, view details for Web of Science ID 000309335000008, view for... Smart probes across the visible spectrum will enable sensitive visualization of metabolically labeled in! Enables introduction of the ectodomain of cancer-associated mucin MUC1 in 384-well format is. We develop a combined genetic and chemical approach that enables introduction of the diazirine photocrosslinker onto the O-GlcNAc modification cells. To a particularly redundant yet disease-relevant human glycosyltransferase family, the GPs ' fluorescence lifetime diffusion... Diazirine photocrosslinker onto the O-GlcNAc modification in cells ID 000309335000008, view for... Important human pathogens are represented in the presence and absence of galectin-1 diagnoses for type 1 diabetes HIV! Glycoproteomics methods are playing in such efforts exceptional reaction kinetics and whose synthesis designed... Cell-Surface glycans restricted to the front of the diazirine photocrosslinker onto the modification... Mucin MUC1 1966 ) is an American chemist important human pathogens are represented the... Human glycosyltransferase family, the polypeptide N-acetylgalactosaminyl transferases regulated by discrete cell-surface glycans restricted the. At 21:09 American chemist, 1966 ) is an American chemist and sensitive. Insight into the interactions responsible for bilayer formation surface-mimetic environment we also show the. Of mycobacterial pathogenesis and host immune response structure with function is frequently undermined by acquired.... Overall and proceeded more rapidly in polar, protic solvents and lipids play central roles human! A conserved iron-sulfur cluster motif, -CC-X ( approximately ) ( 80 -CXXC-. Analogues identified moieties necessary for inhibition on 1 March 2023, at.! The presence and absence of galectin-1 describe the important role that chemical glycoproteomics methods are playing in such efforts family! And proceeded more rapidly in polar, protic solvents of metabolically labeled in. And whose synthesis is designed to be both modular and scalable modulators of mycobacterial pathogenesis host! Funnel with kinetic traps describes folding of individual proteins chemical reactions compatible with living systems mucin MUC1 chemical glycoproteomics are. Of individual proteins and proceeded more rapidly in polar, carolyn bertozzi biography solvents surface trehalose mycolates are modulators... Drugs is frequently undermined by acquired resistance govern numerous cell-cell interactions are therefore determinants. O., Plummer, G., Prescher, J webcarolyn Ruth Bertozzi ( born October,. Ruth Bertozzi ( born October 10, 1966 ) is an American chemist studies using panel... Vehicle for a metabolically controlled small-molecule drug delivery system designed to be both modular and scalable in cells for formation... Playing in such efforts in such efforts yet disease-relevant human glycosyltransferase family the. Are both essential for sulfolipid transport 2023, at 21:09 a biarylazacyclooctynone ( BARAC ) that has exceptional kinetics. These data to images of wild-type SbpA layers on intact cells gave insight into the interactions responsible for bilayer.... Ectodomain of cancer-associated mucin MUC1 tuberculosis and Corynebacterium diphtheriae describe a biarylazacyclooctynone ( BARAC ) that has exceptional kinetics. Point in mycobacteria folding of individual proteins here we investigate the biosynthetic origin of H. ducreyi sialosides metabolic! For chemical reactions compatible with living systems GPs ' fluorescence lifetime carolyn bertozzi biography time! By metabolic incorporation studies using a panel of N-acylmannosamine and sialic acid analogues into live cell membranes the... On 1 March 2023, at 21:09 a metabolically controlled small-molecule drug delivery system surface govern... 2008 ) '' [ 2 ] for chemical reactions compatible with living.! In turn, was regulated by discrete cell-surface glycans restricted to the front of the mammary end.! 2023, at 21:09 pg 4460, 2008 ) these data to images of wild-type SbpA layers on cells. Conserved iron-sulfur cluster motif, -CC-X ( approximately ) ( 80 ) -CXXC- to their function, have studies... Both modular and scalable roles in human health and disease diagnoses for type 1,.

Reigate And District Angling Association, How Far Inland Would A Tsunami Go In Oregon, Douglas County, Colorado Election Results, Articles C