- Semiconductor Quantum Structures and Devices
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- Toxin Mechanisms and Immunotoxins
- Silicon Nanostructures and Photoluminescence
- Protein Structure and Dynamics
- Transgenic Plants and Applications
- Photosynthetic Processes and Mechanisms
- RNA modifications and cancer
- Semiconductor materials and interfaces
- Quantum and electron transport phenomena
- Biochemical and Molecular Research
- Advanced Semiconductor Detectors and Materials
- SARS-CoV-2 and COVID-19 Research
- Photonic and Optical Devices
- Microbial Applications in Construction Materials
- Endoplasmic Reticulum Stress and Disease
- Cellular transport and secretion
- Plant Virus Research Studies
- Helicobacter pylori-related gastroenterology studies
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Plant tissue culture and regeneration
- Chalcogenide Semiconductor Thin Films
- Legume Nitrogen Fixing Symbiosis
Kiang Wu Hospital
2025
Chinese University of Hong Kong
2015-2024
Agrobiotechnology Institute
2023
Hong Kong University of Science and Technology
2007-2010
University of Hong Kong
2007-2010
Pennsylvania State University
2005
Medical Research Council
1996-2003
University of Cambridge
1996-2003
University of Washington
1998-2000
Newcastle University
1987-1996
Most of the oncogenic mutations in tumor suppressor p53 map to its DNA-binding (core) domain. It is thus a potential target cancer therapy for rescue by drugs. To begin understand how mutation inactivates and hence provide structural basis drug design, we have compared structures wild-type mutant core domains solution NMR spectroscopy. Structural changes introduced five hot-spot (V143A, G245S, R248Q, R249S, R273H) were monitored chemical-shift changes. Only localized are observed R273H,...
Most thermophilic proteins tend to have more salt bridges, and achieve higher thermostability by up-shifting broadening their protein stability curves. While the stabilizing effect of salt-bridge has been extensively studied, experimental data on how influences curves are scarce. Here, we used double mutant cycles determine temperature-dependency pair-wise interaction energy contribution salt-bridges ΔCp in a ribosomal L30e. Our results showed that energies for E6/R92 E62/K46 were...
Structural and biochemical study of urease accessory protein complex provides mechanistic insights into the delivery nickel to metalloenzyme urease, an enzyme enabling survival Helicobacter pylori in human stomach.
The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome 2 (SARS-CoV-2), is a global threat to human health. Using multidisciplinary approach, we identified and validated hepatitis C virus (HCV) protease inhibitor simeprevir as an especially promising repurposable drug for treating COVID-19. Simeprevir potently reduces SARS-CoV-2 viral load multiple orders magnitude synergizes with remdesivir in vitro. Mechanistically, showed that not only inhibits...
Apart from prevention using vaccinations, the management options for COVID-19 remain limited. In retrospective cohort studies, use of famotidine, a specific oral H2 receptor antagonist (antihistamine), has been associated with reduced risk intubation and death in patients hospitalized COVID-19. case series, nonhospitalized experienced rapid symptom resolution after taking but molecular basis these observations remains elusive. Here we show biochemical, cellular, functional assays that...
Previous experimental and theoretical studies have produced high-resolution descriptions of the native folding transition states chymotrypsin inhibitor 2 (CI2). In similar fashion, here we use a combination NMR experiments molecular dynamics simulations to examine conformations populated by CI2 in denatured state. The state is highly unfolded, but there some residual helical structure along with hydrophobic clustering center chain. lack persistent nonnative reduces barriers that must be...
Estrogen receptor-related receptors (ERRs; alpha, beta, gamma) are orphan nuclear and constitutively active without binding to estrogen. Like estrogen (ERs), ERRs bind receptor elements element-related repeats. Growing evidence suggests that can cross-talk with ERs in different cell types via competition for DNA sites coactivators. We hypothesize might play regulatory roles normal neoplastic prostatic cells by sharing similar ER-mediated pathways or acting independently. In this study, we...
Background Coronaviruses (CoVs) can be classified into alphacoronavirus (group 1), betacoronavirus 2), and gammacoronavirus 3) based on diversity of the protein sequences. Their 3C-like protease (3CLpro), which catalyzes proteolytic processing polyproteins for viral replication, is a potential target anti-coronaviral infection. Methodology/Principal Findings Here, we profiled substrate specificities 3CLpro from human CoV NL63 OC43 2a), severe acute respiratory syndrome coronavirus (SARS-CoV)...
Significance The underlying mechanisms causing the functional diversity of small GTPase Sar1 paralogs in coat protein complex II-mediated endoplasmic reticulum (ER) export remain elusive higher organisms. Arabidopsis contains five homologs. In this study, we show that AtSar1a exhibits a distinct localization and effects on ER cargo plants through unique interaction with COPII AtSec23a. This specific pairing is required for function under stress . Our results point to mechanism eukaryotes.
In eukaryotes, secretory proteins traffic from the endoplasmic reticulum (ER) to Golgi apparatus via coat protein complex II (COPII) vesicles. Intriguingly, during nutrient starvation, COPII machinery acts constructively as a membrane source for autophagosomes autophagy maintain cellular homeostasis by recycling intermediate metabolites. higher plants, essential roles of have been implicated in plant development and stress responses. Nonetheless, sources autophagosomes, especially...
Residual structure in the denatured state of a protein may contain clues about early events folding. We have simulated by molecular dynamics barnase, which has been studied NMR spectroscopy. An ensemble 10 4 structures was generated after 2 ns unfolding and following for further ns. The heterogeneous, but there nonrandom, residual with persistent interactions. Helical C-terminal portion helix α1 (residues 13–17) α2 as well turn nonnative hydrophobic clustering between β3 β4 were observed,...
We report pseudopotential calculations of the electronic structure a ${\mathrm{Si}}_{4}$${\mathrm{Ge}}_{4}$(001) superlattice grown on Si substrate. Our results show that it is possible to account for observed optical spectra, without invoking indirect transitions, in terms model which microscopic potential and bond lengths Ge layer are bulklike.
We report pseudopotential calculations concerning the electronic structure of GaAs-${\mathrm{Ga}}_{1\mathrm{\ensuremath{-}}\mathrm{x}}$${\mathrm{Al}}_{\mathrm{x}}$As sawtooth (100) superlattice period 140 A\r{}. present energy levels and electron charge densities confined states compare them with our results for usual quantum-well structure. In both systems we find new resonances large amplitudes at interfaces. Our also shed fresh light upon microscopic origin confinement effect.
Background The 3C-like protease (3CLpro) of severe acute respiratory syndrome-coronavirus is required for autoprocessing the polyprotein, and a potential target treating coronaviral infection. Methodology/Principal Findings To obtain thorough understanding substrate specificity protease, library 198 variants was created by performing saturation mutagenesis on autocleavage sequence at P5 to P3' positions. sequences were inserted between cyan yellow fluorescent proteins so that cleavage rates...
Background Thermophilic enzymes are often less active than their mesophilic homologues at low temperatures. One hypothesis to explain this observation is that the extra stabilizing interactions increase rigidity of thermophilic and hence reduce activity. Here we employed a acylphosphatase from Pyrococcus horikoshii its homologous human as model study how local an active-site residue affects enzymatic Methods Findings Acylphosphatases have unique structural feature conserved arginine forms...
The cancer cells can acquire migration and invasion capacities during the metastasis process through developmental regulatory program epithelial–mesenchymal-transition (EMT), its reverse mesenchymal–epithelial transition recolonize at distant metastatic sites. Among multifaceted effects exerted by this program, reorganization of actin cytoskeleton is key mechanical drive for invasive properties gained cells. Collapsin response mediator protein-1 (CRMP1) a cytosolic phosphoprotein originally...
In this study, we examined the anti-Helicobactor pylori effects of main protoberberine-type alkaloids in Rhizoma Coptidis. Coptisine exerted varying antibacterial and bactericidal against three standard H. strains eleven clinical isolates, including four drug-resistant strains, with minimum inhibitory concentrations ranging from 25 to 50 μg/mL minimal 37.5 125 μg/mL. Coptisine's anti-H. derived specific inhibition urease vivo. vitro, coptisine inactivated a concentration-dependent manner...
Abstract Eukaryotic messenger RNA (mRNA) typically contains a methylated guanosine (m 7 G) cap, which mediates major steps of mRNA metabolism. Recently, some RNAs in both prokaryotic and eukaryotic organisms have been found to carry non-canonical cap such as the NAD cap. Here we report that Arabidopsis DXO family protein AtDXO1, was previously known be decapping enzyme for NAD-capped (NAD-RNA), is an essential component m G capping. AtDXO1 associates with activates guanosine-7...