A5091120786- Microbial Natural Products and Biosynthesis
- Chemical Synthesis and Analysis
- Synthetic Organic Chemistry Methods
- RNA Research and Splicing
- Peroxisome Proliferator-Activated Receptors
- Marine Sponges and Natural Products
- Click Chemistry and Applications
- Inflammatory mediators and NSAID effects
- Receptor Mechanisms and Signaling
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- Plant biochemistry and biosynthesis
- Carbohydrate Chemistry and Synthesis
- Microbial Community Ecology and Physiology
- Chemical synthesis and alkaloids
- Enzyme Catalysis and Immobilization
- RNA Interference and Gene Delivery
- Ubiquitin and proteasome pathways
- Glycosylation and Glycoproteins Research
- Peptidase Inhibition and Analysis
- Microbial Metabolic Engineering and Bioproduction
- Antimicrobial Peptides and Activities
University of California, San Diego
2015-2024
Xenobe Research Institute
2014-2024
Salk Institute for Biological Studies
2009-2021
UC San Diego Health System
2019-2021
University of California System
2012-2020
Howard Hughes Medical Institute
2009-2019
University of Arizona
2015-2016
University of California, Irvine
2005-2016
Universidade Federal do Ceará
2014
Purdue University West Lafayette
2011
Genetic studies in Arabidopsis implicate an α/β-hydrolase, KARRIKIN-INSENSITIVE 2 (KAI2) as a receptor for karrikins, germination-promoting butenolide small molecules found the smoke of burned plants. However, direct biochemical evidence interaction between KAI2 and karrikin mechanism downstream signaling by KAI2–karrikin complex remain elusive. We report crystallographic analyses ligand-binding experiments recognition karrikins. The karrikin-1 (KAR 1 ) ligand sits opening to active site...
The NRF2 pathway activates a cell survival response when cells are exposed to xenobiotics or under oxidative stress. Therapeutic activation of can also be used prior insult as means disease prevention. However, prolonged expression has been shown protect cancer by inducing the metabolism and efflux chemotherapeutics, leading both intrinsic acquired chemoresistance drugs. This effect termed “dark side” NRF2. In an effort combat this chemoresistance, our group discovered first inhibitor,...
Adenosine deaminase acting on RNA1 (ADAR1) preserves genomic integrity by preventing retroviral integration and retrotransposition during stress responses. However, inflammatory-microenvironment-induced ADAR1p110 to p150 splice isoform switching drives cancer stem cell (CSC) generation therapeutic resistance in 20 malignancies. Previously, predicting ADAR1p150-mediated malignant RNA editing represented a significant challenge. Thus, we developed lentiviral ADAR1 splicing reporters for...
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTStereoselective Synthesis of β-Mannopyranosides via the Temporary Silicon Connection MethodGilbert Stork and James J. La ClairView Author Information Department Chemistry, Columbia University New York, York 10027Cite this: Am. Chem. Soc. 1996, 118, 1, 247–248Publication Date (Web):January 10, 1996Publication History Received18 September 1995Published online10 January 1996Published inissue 1...
The targeting of marinopyrrole A to actin was identified using a fluorescent dye transfer strategy. process began by appending carboxylic acid terminal tag phenol in the natural product. resulting probe then studied live cells verify that it maintained activity comparable A. Two-color fluorescence microscopy confirmed both unlabeled and labeled materials share uptake subcellular localization HCT-116 cells. Subsequent immunoprecipitation studies as putative target cells, result validated mass...
The protein target of the ammosamides, cytotoxic natural products from a marine-derived actinomycete, has been elucidated. An immunoaffinity fluorescent tag was used to construct molecular probe (see structure). First, uptake and localization in cells visualized with fluorescence microscopy. then co-immunoprecipitate proteins that bound ammosamide core. Myosin thus identified as target. Detailed facts importance specialist readers are published "Supporting Information". Such documents...
RNA splicing plays a fundamental role in human biology. Its relevance cancer is rapidly emerging as demonstrated by spliceosome mutations that determine the prognosis of patients with hematologic malignancies. We report studies using FD-895 and pladienolide-B primary leukemia cells derived from chronic lymphocytic leukemia-lymphoma cell lines. found induce an early pattern mRNA intron retention - modulation. This process was associated apoptosis preferentially compared to normal lymphocytes....
Carbon-carbon bond forming reactions are essential transformations in natural product biosynthesis. During de novo fatty acid and polyketide biosynthesis, β-ketoacyl-acyl carrier protein (ACP) synthases (KS), catalyze this process via a decarboxylative Claisen-like condensation reaction. KSs must recognize multiple chemically distinct ACPs choreograph ping-pong mechanism, often an iterative fashion. Here, we report crystal structures of substrate mimetic bearing complex with the elongating...
We demonstrate site-specific reporter labeling of proteins within live cells. By accessing the coenzyme A (CoA) metabolic pathway with a cell-permeable pantetheine analogue, we deliver CoA-bound molecules for post-translational protein modification in vivo. These methods may be applied to natural product manipulation as well applications conventional molecular and cellular biology.
The peroxisome proliferator-activated receptor (PPAR) family comprises three subtypes: PPARα, PPARγ, and PPARδ. PPARδ transcriptionally modulates lipid metabolism the control of energy homeostasis; therefore, agonists are promising agents for treating a variety metabolic disorders. In present study, we develop panel rationally designed agonists. modular motif affords efficient syntheses using building blocks optimized interactions with subtype-specific residues in ligand-binding domain...
Significance The advance of new clinical treatment options for cancer relies heavily on the discovery chemotherapeutic agents with modes action. In this paper, we describe a potent melanoma-selective agent, seriniquinone, and elucidate its targeting dermcidin dermcidin-conjugated proteins within tumor cells. Early evidence indicates direct correlation between seriniquinone activity levels an ascribed cell line, therein suggesting not only unique target avenue further therapeutic exploration...
Pediatric acute myeloid leukemia (pAML) is typified by high relapse rates and a relative paucity of somatic DNA mutations. Although seminal studies show that splicing factor mutations mis-splicing fuel therapy-resistant stem cell (LSC) generation in adults, deregulation has not been extensively studied pAML. Herein, we describe single-cell proteogenomics analyses, transcriptome-wide analyses FACS-purified hematopoietic progenitor cells followed differential dual-fluorescence lentiviral...
A centralized method for studying natural product chemical biology begins by designating a single fluorescent dye as core reporter and develops through the facile conversion to diverse panel of fluorescently labeled products. Comparative analyses are developed using LED fluorescence microscopy. Application this is established profiling cellular uptake localization selected members anthracycline, acetogenin, depsipeptide, nonribosomal peptide, polyether, polyketide families
Steroids play fundamental roles regulating mammalian reproduction and development. Although sex steroids their receptors are well characterized in vertebrates several arthropod invertebrates, little is known about the hormones other invertebrate species. Evolutionary insights into ancient endocrine pathways can be gained by elucidating functioning reproduction. Using a combination of genomic analyses, receptor imaging, ligand identification, target elucidation, exploration function through...
Extracts of Ganoderma tsugae, also known as the Hemlock varnish shelf mushroom, and related Reishi mushrooms are well documented in traditional Chinese medicine. Several sp. currently cultivated for use coffee, teas, dietary supplements. We now report on isolation characterization an unprecedented benzofuran, ganodone (1), from fruiting bodies mature growth G. tsugae. This discovery provides a key next step evaluating active components their associated herbal
The full monty: recently discovered thiol cofactor bacillithiol (BSH), its biosynthetic precursors, and symmetrical disulfide are prepared in two ways. fosfomycin resistance protein (FosB) is shown to be a BSH-utilizing enzyme. It displays bacillithiol-S-transferase activity with strong preference for BSH over L-cysteine as substrate. Detailed facts of importance specialist readers published "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They made...