A5050667730- Cancer, Hypoxia, and Metabolism
- Biochemical and Molecular Research
- RNA modifications and cancer
- Amino Acid Enzymes and Metabolism
- Glycosylation and Glycoproteins Research
- Enzyme Structure and Function
- Cancer Research and Treatments
- Chemical Synthesis and Characterization
- Pesticide and Herbicide Environmental Studies
- MicroRNA in disease regulation
- Extracellular vesicles in disease
- RNA Interference and Gene Delivery
- Pesticide Exposure and Toxicity
- Radioactive element chemistry and processing
- Insect and Pesticide Research
- Epigenetics and DNA Methylation
- Molecular Sensors and Ion Detection
- Metabolomics and Mass Spectrometry Studies
- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
Cornell University
2019-2024
Korea Advanced Institute of Science and Technology
2016-2017
A new 1,8-naphthalimide-based fluorescent probe for the detection of diethyl cyanophosphonate, a very common nerve agent simulant, is designed, synthesized, and characterized fully. The shows around 50-fold enhancement fluorescence intensity over other simulants. Importantly, able to work under aqueous conditions in wide pH range. Two reactive groups, oxime phenol, allow dual emission with different kinetic reactions. reaction cyanophosphonate group occurs advance; resulting time response...
Mutations in KRAS frequently occur human cancer and are especially prevalent pancreatic ductal adenocarcinoma (PDAC), where they have been shown to promote aggressive phenotypes. However, targeting this onco-protein has proven be challenging, highlighting the need further identify various mechanisms used by drive progression. Here, we considered role played exosomes, a specific class of extracellular vesicles (EVs) derived from endocytic cellular trafficking machinery, mediating ability cell...
Cancer cells frequently exhibit uncoupling of the glycolytic pathway from TCA cycle (i.e., "Warburg effect") and as a result, often become dependent on their ability to increase glutamine catabolism. The mitochondrial enzyme Glutaminase C (GAC) helps satisfy this 'glutamine addiction' cancer by catalyzing hydrolysis glutamate, which is then converted TCA-cycle intermediate α-ketoglutarate. This makes GAC an intriguing drug target spurred molecules derived...
The glutaminase enzymes GAC and GLS2 catalyze the hydrolysis of glutamine to glutamate, satisfying 'glutamine addiction' cancer cells. They are targets anti-cancer drugs; however, their mechanisms activation catalytic activity have been unclear. Here we demonstrate that ability form filaments is directly coupled present cryo-EM structures which provide a view conformational states essential for catalysis. Filament formation guides an 'activation loop' assume specific conformation works...
The mitochondrial enzyme glutaminase C (GAC) is upregulated in many cancer cells to catalyze the first step glutamine metabolism, hydrolysis of glutamate. dependence on this transformed metabolic pathway highlights GAC as a potentially important therapeutic target. acquires maximal catalytic activity upon binding anionic activators such inorganic phosphate. To delineate mechanism activation, we used tryptophan substitution tyrosine 466 site fluorescent reporter for presence and absence We...
The glutaminase C (GAC) isoform of mitochondrial is overexpressed in many cancer cells and therefore represents a potential therapeutic target. Understanding the regulation GAC activity has been guided by development spectroscopic approaches that measure real time. Previously, we engineered protein (GAC(F327W)) which tryptophan residue substituted for phenylalanine an activation loop to explore role this enzyme activity. We showed fluorescence emission Trp-327 enhanced response activator...
The glutaminase enzymes GAC and GLS2 catalyze the hydrolysis of glutamine to glutamate, satisfying 'glutamine addiction' cancer cells. They are targets anti-cancer drugs; however, their mechanisms activation catalytic activity have been unclear. Here we demonstrate that ability form filaments is directly coupled present cryo-EM structures which provide an unprecedented view conformational states essential for catalysis. Filament formation guides 'activation loop' assume a specific...
Abstract Many cancer cells become dependent on glutamine metabolism to compensate for glycolysis being uncoupled from the TCA cycle. The mitochondrial enzyme Glutaminase C (GAC) satisfies this ‘glutamine addiction’ by catalyzing first step in metabolism, making it an attractive drug target. Despite one of allosteric inhibitors (CB-839) clinical trials, none drugs targeting GAC are approved treatment and their mechanism action is not well understood. A major challenge has been rational design...