A5048570287- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Glycosylation and Glycoproteins Research
- Receptor Mechanisms and Signaling
- Galectins and Cancer Biology
- Mass Spectrometry Techniques and Applications
- Carbohydrate Chemistry and Synthesis
- Ubiquitin and proteasome pathways
- Chemical Synthesis and Analysis
- Biochemical and Molecular Research
- Enzyme Structure and Function
- Coordination Chemistry and Organometallics
- Asymmetric Synthesis and Catalysis
- Synthetic Organic Chemistry Methods
- Neuropeptides and Animal Physiology
- Protein Kinase Regulation and GTPase Signaling
- Organometallic Complex Synthesis and Catalysis
- Monoclonal and Polyclonal Antibodies Research
- Chemical Synthesis and Reactions
- Catalytic Cross-Coupling Reactions
- Cellular transport and secretion
- Proteoglycans and glycosaminoglycans research
- Biochemical and Structural Characterization
- RNA Interference and Gene Delivery
- Microbial Natural Products and Biosynthesis
University of Colorado Anschutz Medical Campus
2025
University of Montana
2025
Stanford University
2016-2024
Harvard University
2013-2024
University of Toronto
2008-2014
Davenport University
2011
O-GlcNAc transferase (OGT) is an essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins. Its targets include kinases, phosphatases, transcription factors, histones, many other intracellular The biology modification still not well understood, cell-permeable inhibitors OGT are needed both as research tools for validating a therapeutic target. Here, we report small...
Dual-Duty Active Site O-linked N-acetylglucosamine transferase (OGT) catalyzes the addition of (GlcNac) to serine or threonine residues, influencing localization and function proteins. Because its activity is sensitive nutrient uridine diphosphate (UDP)–GlcNac, OGT has been proposed regulate cellular responses status. Recently, in presence UDP-GlcNac was shown cleave host cell factor–1 (HCF-1), a transcriptional coregulator human cell-cycle progression. This cleavage required for HCF-1...
Reversible glycosylation of nuclear and cytoplasmic proteins is an important regulatory mechanism across metazoans. One enzyme, O-linked N-acetylglucosamine transferase (OGT), responsible for all nucleocytoplasmic there a well-known need potent, cell-permeable inhibitors to interrogate OGT function. Here we report the structure-based evolution culminating in compounds with low nanomolar inhibitory potency on-target cellular activity. In addition disclosing useful inhibitors, structures...
Binding of arrestin to phosphorylated G protein-coupled receptors (GPCRs) is crucial for modulating signaling. Once internalized, some GPCRs remain complexed with β-arrestins, while others interact only transiently; this difference affects GPCR signaling and recycling. Cell-based in vitro biophysical assays reveal the role membrane phosphoinositides (PIPs) β-arrestin recruitment GPCR-β-arrestin complex dynamics. We find that broadly stratify into two groups, one requires PIP binding does...
The problem of antibiotic resistance has prompted the search for new antibiotics with novel mechanisms action. Analogues A54556 cyclic acyldepsipeptides (ADEPs) represent an attractive class antimicrobial agents that act through dysregulation caseinolytic protease (ClpP). Previous studies have shown ADEPs are active against Gram-positive bacteria (e.g., MRSA, VRE, PRSP (penicillin-resistant Streptococcus pneumoniae)); however, there currently few examining Gram-negative bacteria. In this...
G protein-coupled receptors (GPCRs) are the largest class of integral membrane and responsible for transmitting diverse signals in response to extracellular stimuli. Post-translational modifications serve dictate subcellular trafficking function a GPCR across space time. Despite significant interest mapping diversity modification states (proteoforms), technical challenges have hindered this characterization. While advancements mimetics mass spectrometry instrumentation improved analysis,...
G protein-coupled receptors (GPCRs) are the largest class of integral membrane and responsible for transmitting diverse signals in response to extracellular stimuli. Post-translational modifications serve dictate subcellular trafficking function a GPCR across space time. Despite significant interest mapping diversity modification states (proteoforms), technical challenges have hindered this characterization. While advancements mimetics mass spectrometry instrumentation improved analysis,...
Glycosylation of nuclear and cytoplasmic proteins is an essential post-translational modification in mammals. O-GlcNAc transferase (OGT), the sole enzyme responsible for this modification, glycosylates more than 1000 unique substrates. How OGT selects its substrates a fundamental question that must be answered to understand OGT's unusual biology. contains long tetratricopeptide repeat (TPR) domain has been implicated substrate selection, but there almost no information about how changes...
O-GlcNAc transferase (OGT) is an essential mammalian enzyme that glycosylates myriad intracellular proteins and cleaves the transcriptional coregulator Host Cell Factor 1 to regulate cell cycle processes. Via these catalytic activities as well noncatalytic protein–protein interactions, OGT maintains homeostasis. OGT’s tetratricopeptide repeat (TPR) domain important in substrate recognition, but there little information on how changing TPR impacts its cellular functions. Here, we investigate...
A practical method for the chemo- and diastereoselective allylation of α,β-epoxy ketones has been developed by using convenient air moisture stable reagent potassium allyltrifluoroborate. Indium metal was found to promote addition in stoichiometric or catalytic amounts, afford α,β-epoxyhomoallylic tertiary alcohols high yields diastereoselectivities, without competing ring-scission epoxide.
The stereoselective synthesis of (+)-antimycin A1b has been accomplished in 12 linear steps and 18% overall yield from (−)-ethyl lactate. A robust, scalable, highly diastereoselective montmorillonite K10-promoted allylation reaction between an α-silyloxy aldehyde a substituted potassium allyltrifluoroborate salt provides general approach to the core stereochemical triad antimycin family. requisite (Z)-substituted was synthesized using syn-selective hydroboration/protodeboration...
O-Linked β-N-acetylglucosamine transferase (OGT) is an essential human enzyme that glycosylates numerous nuclear and cytoplasmic proteins on serine threonine. It also cleaves Host cell factor 1 (HCF-1) by a mechanism in which the first step involves glycosylation glutamate. Replacing glutamate with aspartate HCF-1 proteolytic repeat was shown to prevent peptide backbone cleavage, but whether occurred not examined. We report here OGT much faster than it otherwise identical model substrate;...
We report the formation of an unexpected trinuclear palladium beta-diiminate complex from decomposition [Pd(Ph(2)nacnac)(Cl)(4-H(2)NC(6)H(4)-(t)Bu)] (nacnac = derived acetylacetone), proposed reaction pathway, and synthesis first dinuclear with amido-chloro double-bridge.
Summary Binding of arrestin to phosphorylated G protein-coupled receptors (GPCRs) is crucial for modulating signaling. Once internalized some GPCRs may complex with arrestin, while others interact transiently; this difference affects receptor signaling and recycling. Cell-based in vitro biophysical assays reveal the role membrane phosphoinositides (PIPs) recruitment GPCR-arrestin dynamics. We find that broadly stratify into two groups, one requiring PIP-binding does not. Plasma PIPs...
<b>Abstract ID 99322</b> <b>Poster Board 558</b> G protein-coupled receptors (GPCRs) are a family of seven transmembrane proteins that function to transduce extracellular signals, such as hormones and neurotransmitters, into intracellular signals. To achieve temporal regulation signaling, known ß-arrestins responsible for terminating protein-mediated signaling desensitizing receptors. These ß-arrestin also mediating the internalization most GPCRs, thus dictating their recycling...
Abstract The assembly of a peptide ligand, its receptor, and β-arrestin (βarr) into ternary complex within the cell membrane is crucial aspect G protein-coupled receptor (GPCR) signaling. We explore this by attaching fluorescent moieties to parathyroid hormone (PTH) type 1 (PTH R), using PTH as prototypical hormone, along with βarr clathrin, recording dual-color single-molecule imaging at plasma live cells. Here we show that R exhibits near-Brownian diffusion, whereas unbound displays...
Abstract The regioselective reaction requires a stoichiometric amount of In to achieve high yields and diastereoselectivity the ratio CH 2 Cl /H O plays significant role.