A5055980370- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Toxin Mechanisms and Immunotoxins
- Transgenic Plants and Applications
- Protein Structure and Dynamics
- Polyamine Metabolism and Applications
- Diet, Metabolism, and Disease
- Biochemical and Molecular Research
- Enzyme Structure and Function
- Cancer, Hypoxia, and Metabolism
- Bacteriophages and microbial interactions
- DNA Repair Mechanisms
- Microtubule and mitosis dynamics
- Plant Virus Research Studies
- Ocular Oncology and Treatments
- Photosynthetic Processes and Mechanisms
- Click Chemistry and Applications
- Genomics and Chromatin Dynamics
- Plant Parasitism and Resistance
- Pharmacological Effects of Natural Compounds
- RNA and protein synthesis mechanisms
- Plant and animal studies
- Amino Acid Enzymes and Metabolism
- French Urban and Social Studies
- X-ray Diffraction in Crystallography
California State University, San Bernardino
2023-2025
Salk Institute for Biological Studies
2016-2019
Howard Hughes Medical Institute
2016-2019
University of California, Santa Cruz
2010-2016
University of Toronto
2009-2010
The perception mechanism for the strigolactone (SL) class of plant hormones has been a subject debate because their receptor, DWARF14 (D14), is an α/β-hydrolase that can cleave SLs. Here we show via time-course analyses SL binding and hydrolysis by Arabidopsis thaliana D14, level uncleaved strongly correlates with induction active signaling state. In addition, AtD14
Cyclin-dependent kinase (Cdk) phosphorylation of the Retinoblastoma protein (Rb) drives cell proliferation through inhibition Rb complexes with E2F transcription factors and other regulatory proteins. We present first structures phosphorylated that reveal mechanism its inactivation. S608 orders a flexible “pocket” domain loop such it mimics directly blocks transactivation (E2F TD ) binding. T373 induces global conformational change associates pocket N-terminal domains (RbN). This multidomain...
Chalcone isomerase–like (CHIL) protein is a noncatalytic that enhances flavonoid content in green plants by serving as metabolite binder and rectifier of chalcone synthase (CHS). Rectification CHS catalysis occurs through direct protein–protein interactions between CHIL CHS, which alter kinetics product profiles, favoring naringenin (NC) production. These discoveries raise questions about how proteins interact structurally with metabolites CHIL–ligand affect CHS. Using differential scanning...
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Chalcone isomerases are plant enzymes that perform enantioselective oxa-Michael cyclizations of 2′-hydroxychalcones into flavanones. An X-ray crystal structure an enzyme–product complex combined with molecular dynamics simulations reveal enzyme mechanism wherein the guanidinium ion a conserved arginine positions nucleophilic phenoxide and activates electrophilic enone for cyclization through Brønsted Lewis acid interactions. The reaction terminates by asymmetric protonation carbanion...
The retinoblastoma (Rb) tumor suppressor protein negatively regulates cell proliferation by binding and inhibiting E2F transcription factors. Rb inactivation occurs in cancer cells upon cyclin-dependent kinase (Cdk) phosphorylation, which induces release activation of cycle genes. We present a strategy for activating phosphorylated with molecules that bind directly enhance affinity E2F. developed fluorescence polarization assay can detect the effect exogenous compounds on modulating...
The retinoblastoma tumor suppressor (Rb) is a multifunctional protein that primarily regulates the cell cycle but also has roles in cellular differentiation, DNA damage response and apoptosis. loss of Rb key event development or progression many cancers. Essential functions occur through its pocket domain, which necessary for regulating binding interactions with E2F transcription factors repressors bind via an LxCxE motif. domain most highly-conserved region multidomain protein, as well...
By the 1960s, Quebec was poised for change. Two visions of a modern began to emerge that clashed throughout decade, culminating in what has become known as Canada’s most significant encounter with terrorism: October Crisis. While newly elected Liberal government pushed forward social and economic reforms, Front de Libération du Québec (FLQ) emerged different vision characterized by independence socialism. This article argues modernization comes geographical transformation violence. It looks...
Abstract The emergence of catalysis in a non-catalytic protein scaffold is rare, unexplored event. Chalcone isomerase (CHI), key enzyme plant flavonoid biosynthesis, presumed to have evolved from non-enzymatic ancestor related the widely-distributed fatty-acid binding proteins (FAPs) and family with no activity (CHILs for “CHI-like”). Ancestral inference confirmed that CHI lacking activity. We also identified four alternative founder mutations, i.e. mutations individually instated activity,...
Chalcone Isomerase (CHI) evolved from a non‐enzymatic Fatty Acid‐binding protein (FAP) into highly‐efficient catalyst for the stereospecific conversion of naringenin chalcone (2S)‐naringenin, an early committed step plant flavanoid pathway. To understand structural basis emergence and evolution enzyme activity in CHI, we reconstructed probable ancestor which represents form that has yet to acquire canonical CHI activity. Directed this “ancestral” uncovered three substitutions, each are...
Abstract Chalcone isomerases are plant enzymes that perform enantioselective oxa-Michael cyclizations of 2′-hydroxy-chalcones into flavanones. An X-ray crystal structure an enzyme-product complex and molecular dynamics simulations reveal enzyme mechanism wherein the guanidinium ion a conserved arginine positions nucleophilic phenoxide activates electrophilic enone for cyclization through Brønsted Lewis acid interactions. The reaction terminates by asymmetric protonation carbanion...
In organic synthesis, bifunctional chiral catalysts are an increasingly popular tool to position and stabilize a nucleophile activate electrophile for asymmetric addition reactions. It turns out that chemists were not first employ this synthetic strategy, plants have been using similar method quite some time (~500 million years). By techniques in structural biology, enzymology NMR, we characterize novel mechanism by which the enzyme chalcone isomerase (CHI) catalyzes oxa‐Michael cyclizations...