A5090652990- Biochemical and Molecular Research
- Metalloenzymes and iron-sulfur proteins
- Genomics, phytochemicals, and oxidative stress
- Carbohydrate Chemistry and Synthesis
- Porphyrin Metabolism and Disorders
- CO2 Reduction Techniques and Catalysts
- Sirtuins and Resveratrol in Medicine
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Pneumocystis jirovecii pneumonia detection and treatment
- Fungal and yeast genetics research
- Advanced biosensing and bioanalysis techniques
- Peptidase Inhibition and Analysis
- Chemical Synthesis and Analysis
- Adipose Tissue and Metabolism
- Protist diversity and phylogeny
- Cancer therapeutics and mechanisms
- Nanopore and Nanochannel Transport Studies
- Synthesis and Biological Evaluation
- Korean Urban and Social Studies
- Nitrogen and Sulfur Effects on Brassica
- Computational Drug Discovery Methods
- RNA modifications and cancer
- Plant Stress Responses and Tolerance
- Biosensors and Analytical Detection
The University of Texas at Austin
2014-2025
Korea Institute of Science and Technology
2024
Scripps (United States)
2019-2023
Scripps Institution of Oceanography
2019-2023
Scripps Research Institute
2018-2023
Torrey Pines Institute For Molecular Studies
2022
Seoul National University
2010-2012
Ewha Womans University
2010
KEAP1 (Kelch-like ECH-associated protein), a cytoplasmic repressor of the oxidative stress responsive transcription factor Nuclear erythroid 2-related 2 (NRF2), senses presence electrophilic agents by modification its sensor cysteine residues. In addition to xenobiotics, several reactive metabolites have been shown covalently modify key cysteines on KEAP1, although full repertoire these molecules and their respective modifications remain undefined. Here, we report discovery sAKZ692, small...
Significance The small size of short ORF-encoded peptides (SEPs) has made it difficult to identify their cellular binding partners using standard methods. Here, we show that the photo-crosslinking amino acid AbK can be incorporated into overexpressed, epitope-tagged SEP transgenes, allowing covalent bond formation between SEPs and interactors in live cells. From an AP-MS–based screen conserved mammalian SEPs, identified histone protein (SEBHP), a micropeptide which acts as transcriptional...
Formycin A is a potent purine nucleoside antibiotic with C-glycosidic linkage between the ribosyl moiety and pyrazolopyrimidine base. Herein, cosmid identified from Streptomyces kaniharaensis genome library that contains for gene cluster responsible biosynthesis of formycin. Subsequent deletion experiments in vitro characterization forBCH products established their catalytic functions formycin biosynthesis. Results also demonstrated PurH de novo plays key role formation during A. The...
It has been hypothesized that mitochondria evolved from a bacterial ancestor initially became established in an archaeal host cell as endosymbiont. Here we model this first stage of mitochondrial evolution by engineering endosymbiosis between Escherichia coli and Saccharomyces cerevisiae An ADP/ATP translocase-expressing E. provided ATP to respiration-deficient cox2 yeast mutant enabled growth yeast-E. chimera on nonfermentable carbon source. In reciprocal fashion, thiamin endosymbiotic...
In this study, a divergent and practical solid-phase parallel diversity-oriented synthesis (DOS) strategy was successfully applied for the construction of five discrete core skeletons embedded with privileged benzopyranyl substructure. The diversity these expanded through introduction various substituents at R, R1, R2 positions from single key intermediate in different pathways. More importantly, we efficiently maximized molecular transformation skeleton itself by using library-to-library...
Formycin A and pyrazofurin are two naturally occurring pyrazole-derived C-nucleosides with antibacterial antiviral activities. While earlier studies have established the chemistry of C-glycosidic bond formation as well subsequent steps in biosynthesis formycin pyrazofurin, how pyrazole ring itself is constructed remains elusive. N-N was previously reported to involve coupling N6-hydroxylated l-lysine l-glutamic acid catalyzed by hydrazine synthetase PyfG, herein PyfG its homologue ForJ shown...
Proteolysis targeting chimeras (PROTACs) enable the selective and sub-stoichiometric elimination of pathological proteins, yet only two E3 ligases are routinely used for this purpose. Here, we expand repertoire PROTAC compatible by identifying a novel small molecule scaffold ubiquitin ligase KLHDC2 using fluorescence polarization-based high throughput screen. We highlight utility ligand with synthesis PROTACs capable potently degrading BRD4 in cells. This work affords additional chemical...
Abstract C ‐Nucleosides are characterized by a C−C rather than C−N linkage between the heterocyclic base and ribofuranose ring. While biosynthesis of pseudouridine‐ ‐nucleosides has been studied, less is known about pyrazole‐ such as formycins pyrazofurin. Herein, genome screening Streptomyces candidus NRRL 3601 led to discovery pyrazofurin biosynthetic gene cluster pyf . In vitro characterization product PyfQ demonstrated that it able catalyze formation ‐glycoside carboxyhydroxypyrazole...
Abstract DesII is a radical S ‐adenosylmethionine (SAM) enzyme that catalyzes the C4‐deamination of TDP‐4‐amino‐4,6‐dideoxyglucose through C3 intermediate. However, if C4 amino group replaced with hydroxy (to give TDP‐quinovose), at oxidized to ketone no C4‐dehydration. It hypothesized hyperconjugation between CN/O bond and partially filled p orbital intermediate modulates degree which elimination competes dehydrogenation. To investigate this hypothesis, reaction C4‐epimer TDP‐quinovose...
Genome scanning of Streptomyces kaniharaensis, the producer formycin A, reveals two sets purA, purB, purC, and purH genes. The Pur enzymes catalyze pyrimidine assembly purine nucleobases. To test whether encoded by second set pur genes analogous transformations in biosynthesis, B 5′-phosphate was synthesized shown to be converted ForA ForB A 5′-phosphate. These results support that For are responsible for formation.
Based on the endosymbiotic theory, one of key events that occurred during mitochondrial evolution was an extensive loss nonessential genes from protomitochondrial endosymbiont genome and transfer some essential to host nucleus. We have developed approach recapitulate various aspects minimization using a synthetic system consisting Escherichia coli endosymbionts within yeast cells. As first step, we identified number E. auxotrophs central metabolites can form viable These studies provide...
Lymphocyte-specific protein tyrosine kinase (Lck) plays vital roles in the T-cell receptor- mediated development, function, and differentiation of T-cells. Given its substantial involvement T cell signaling, irregularities expression functionality Lck may lead to various diseases, including cancer. In this study, we found that compound 12a exerted significant inhibitory potency against with an IC50 value 10.6 nM. addition, demonstrated high efficacy colon cancer lines as indicated by GI50...
Significance Coformycin and pentostatin are potent nucleoside inhibitors of adenosine deaminase with anticancer activity due to their structurally unique 1, 3-diazepine nucleobases. Herein, the biosynthetic pathway coformycin is reconstituted in vitro, demonstrating that it directly overlaps early stages l -histidine biosynthesis. The key branch point between pathways involves a seven-membered ring cyclization reaction likely proceeds via Dieckmann retro-aldol elimination. This catalyzed an...
Abstract DesII is a radical S ‐adenosylmethionine (SAM) enzyme that catalyzes the C4‐deamination of TDP‐4‐amino‐4,6‐dideoxyglucose through C3 intermediate. However, if C4 amino group replaced with hydroxy (to give TDP‐quinovose), at oxidized to ketone no C4‐dehydration. It hypothesized hyperconjugation between CN/O bond and partially filled p orbital intermediate modulates degree which elimination competes dehydrogenation. To investigate this hypothesis, reaction C4‐epimer TDP‐quinovose...
Spectinomycin is a dioxane-bridged, tricyclic aminoglycoside produced by Streptomyces spectabilis ATCC 27741. While the spe biosynthetic gene cluster for spectinomycin has been reported, chemistry underlying construction of dioxane ring unknown. The twitch radical SAM enzyme SpeY from shown here to catalyze dehydrogenation C2′ alcohol (2′R,3′S)-tetrahydrospectinomycin yield (3′S)-dihydrospectinomycin as likely intermediate. This reaction radical-mediated and initiated via H atom abstraction...
Abstract C ‐Nucleosides are characterized by a C−C rather than C−N linkage between the heterocyclic base and ribofuranose ring. While biosynthesis of pseudouridine‐ ‐nucleosides has been studied, less is known about pyrazole‐ such as formycins pyrazofurin. Herein, genome screening Streptomyces candidus NRRL 3601 led to discovery pyrazofurin biosynthetic gene cluster pyf . In vitro characterization product PyfQ demonstrated that it able catalyze formation ‐glycoside carboxyhydroxypyrazole...
Summary Autophagy-lysosomal impairment is an early and prominent feature of neurodegeneration. Autophagy activation reduces protein aggregates lipid level abnormalities. We performed a high-content imaging-based screen assessing 940,000 small molecules to identify those that reduce droplet numbers. Of 77 validated, structurally diverse hits, 24 increased autophagy flux reporter activity, consistent with accelerated clearance by lipophagy. these, we show CCT020312 activates independently...
We developed fluorescent biosensor systems that are either general or selective to fluoroquinolone antibiotics by using a single-chain variable-fragment (scFv) as recognition element. The selectivity of these biosensors was rationally tuned through the structural modification on pharmacophore and subsequent selection scFv receptor modules against antibiotics-based antigens phage display. resulting A2 F9 scFv's bound their representative antigen with moderate affinity (K(D) in micromolar...
Crosstalk between metabolism and stress-responsive signaling is essential to maintaining cellular homeostasis. One way this crosstalk achieved through the covalent modification of proteins by endogenous, reactive metabolites that regulate activity key transcription factors such as NRF2. Several including methylglyoxal, glyceraldehyde 3-phosphate, fumarate, itaconate covalently modify sensor cysteines NRF2 regulatory protein KEAP1, resulting in stabilization activation its cytoprotective...
DesII is a radical SAM lyase that catalyzes deamination reaction during the biosynthesis of desosamine in Streptomyces venezuelae. Competing mechanistic hypotheses for this radical-mediated are differentiated according to whether 1,2-migration takes place and timing proton abstraction following generation substrate α-hydroxyalkyl intermediate. In study, deuterated C4 epimer natural substrate, TDP-4-amino-4-deoxy-d-[3-2H]fucose, was prepared shown be undergoing alone with specific activity...
A FRET-based high-throughput screening system was developed for the discovery of competitive smallmolecule Hsp90 inhibitors. The biarsenical fluorescein derivative FlAsH and dabcyl-conjugated inhibitor GM were employed as FRET donor quencher, respectively. spatial proximity perturbation between FlAsH-labeled Hsp90N GM-dabcyl upon treatment a small molecule led to changes in FRET-induced fluorescence, monitored fashion.