A5070868483- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Enzyme Structure and Function
- Protein Structure and Dynamics
- Alzheimer's disease research and treatments
- CRISPR and Genetic Engineering
- Adipose Tissue and Metabolism
- FOXO transcription factor regulation
- Medicinal Plants and Neuroprotection
- Bioactive natural compounds
- Apelin-related biomedical research
- Lysosomal Storage Disorders Research
- Multilevel Inverters and Converters
- Machine Learning in Bioinformatics
- Mitochondrial Function and Pathology
- Adipokines, Inflammation, and Metabolic Diseases
- Flavonoids in Medical Research
- Pharmacogenetics and Drug Metabolism
- Microbial Metabolism and Applications
- Porphyrin Metabolism and Disorders
- Amyotrophic Lateral Sclerosis Research
- Sirtuins and Resveratrol in Medicine
- Heat shock proteins research
- Biochemical and Structural Characterization
- Protein Interaction Studies and Fluorescence Analysis
Korea Research Institute of Bioscience and Biotechnology
2014-2023
Korea Research Institute of Chemical Technology
2021-2022
Korea University of Science and Technology
2014-2021
VA Sepulveda Ambulatory Care Center
2001
VA West Los Angeles Medical Center
2001
Geriatric Research Education and Clinical Center
2001
VA Greater Los Angeles Healthcare System
2001
Western Sydney University
1998
ANXA11 dysfunction induces alteration of intracellular Ca 2+ homeostasis and stress granule disassembly in ALS.
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease, distinctively characterized by senile plaques, neurofibrillary tangles, and synaptic loss, finally resulting in neuronal death. β-Site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) cholinesterases have been identified as therapeutic targets for AD, discovery of their inhibitors critical importance developing preventive strategies AD. To discover natural multi-target compounds possessing BACE1,...
One of the major neurodegenerative features Alzheimer's disease (AD) is presence neurotoxic amyloid plaques composed beta peptide (Aβ). β-Secretase (BACE1) and acetylcholinesterase (AChE), which promote Aβ fibril formation, have become attractive therapeutic targets for AD. P-glycoprotein (P-gp), efflux pump blood-brain barrier (BBB), plays a critical role in limiting molecules. In pursuit discovering natural anti-AD candidate, bioactivity, physicochemical, drug-likeness, molecular docking...
Predicting drug response is critical for precision medicine. Diverse methods have predicted responsiveness, as measured by the half-maximal inhibitory concentration (IC50), in cultured cells. Although IC50s are continuous, traditional prediction models dealt mainly with binary classification of responsiveness. However, since there few regression-based IC50 predictions, comprehensive evaluations models, including machine learning (ML) and deep (DL), diverse data types dataset sizes, not been...
Heterogeneity in intratumoral cancers leads to discrepancies drug responsiveness, due diverse genomics profiles. Thus, prediction of responsiveness is critical precision medicine. So far, prediction, drugs' molecular "fingerprints", along with mutation statuses, have not been considered. Here, we constructed a 1-dimensional convolution neural network model, DeepIC50, predict three classes, based on 27,756 features including statuses and various fingerprints. As result, DeepIC50 showed better...
BACE1 is the rate-limiting enzyme involved in production and deposition of β-amyloid (Aβ). Since neurotoxic Aβ plays a critical role Alzheimer’s disease (AD) pathogenesis, has emerged as key target for preventing AD. In present study, potential sulforaphane, an isothiocyanate found cruciferous vegetables, inhibitor been investigated. Sulforaphane exhibited six times more potent activity against compared to well-known positive controls including resveratrol quercetin. presented selective...
This study was to assess the possibility of using competitive and slow binding experiments with affinity-based ultrafiltration UPLC-QTof-MS analysis identify potent bacterial neuraminidase (bNA) inhibitors from Broussonetia papyrifera roots extract. To isolate unbound compounds enzyme-binding complex, root bark extracts were either incubated in absence bNA, presence or time-dependent bNA before performed. Thirteen flavonoids separated target extract, their inhibitory activities tested...
Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) mediate the degradation of acetylcholine (ACh), a primary neurotransmitter in brain. Cholinergic deficiency occurs during progression Alzheimer’s disease (AD), resulting widespread cognitive dysfunction decline. We evaluated potential effect natural cholinesterase inhibitor, zerumbone, using vitro target enzyme assays, as well silico docking ADMET (absorption, distribution, metabolism, excretion, toxicity) simulation. Zerumbone...
Gastric cancer (GC) is a highly heterogeneous disease with few "targeted" therapeutic options. Previously, we demonstrated involvement of the transcription factor HNF4α in human GC tumours, and developmental signal mediator, WNT5A, as prognostic biomarker. One previously developed antagonist, BI6015, while not advancing beyond preclinical stages, remains useful for studying GC. Here, characterised antineoplastic signalling activity derivatives including transfer nitro group from para...
Alzheimers disease (AD) is believed to involve increased soluble but toxic beta amyloid (Aβ) peptide aggregates, leading the accumulation of insoluble Aβ deposits, inflammation, oxidative damage, tau pathology and ultimately cognitive deficits. Blocking formation early should prevent AD, most interventions are likely occur after seeding deposits tangles initiation cascade. In order identify agents that might suppress both response in vivo, we infused into rat ventricles screened targeting...
Melanin-concentrating hormone receptor 1 (MCHR1) has been a target for appetite suppressants, which are helpful in treating obesity. However, it is challenging to develop an MCHR1 antagonist because its binding site similar that of the human Ether-à-go-go-Related Gene (hERG) channel, whose inhibition may cause cardiotoxicity. Most drugs developed as antagonists have failed clinical development due cardiotoxicity caused by hERG inhibition. Machine learning-based prediction models can overcome...
Alzheimer’s disease (AD) is a neurodegenerative conceptualized as clinical-biological construct where amyloid-beta pathophysiology supposed to play role. The loss of cognitive functions mostly characterized by the rapid hydrolysis acetylcholine cholinesterases including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Moreover, both enzymes are responsible for non-catalytic actions such interacting with amyloid β peptide (Aβ) which further leads promote senile plaque formation....
The Forkhead box protein M1 (FoxM1) is an appealing target for anti-cancer therapeutics as this cell proliferation-associated transcription factor overexpressed in most human cancers. FoxM1 involved tumor invasion, angiogenesis, and metastasis. To discover novel inhibitors that disrupt the FoxM1-DNA interaction, we identified CDI, a small molecule inhibits interaction. CDI was through assay based on time-resolved fluorescence energy transfer response of labeled consensus oligonucleotide...
Protein structure refinement is a necessary step for the study of protein function. In particular, some nuclear magnetic resonance (NMR) structures are lower quality than X-ray crystallographic structures. Here, we present NMRe, web-based server NMR refinement. The previously developed knowledge-based energy function STAP (Statistical Torsion Angle Potential) was used NMRe With STAP, provides two protocols using types distance restraints. If user NOE (Nuclear Overhauser Effect) data,...
Abstract Drug repositioning research using transcriptome data has recently attracted attention. In this study, we attempted to identify new target proteins of the urotensin-II receptor antagonist, KR-37524 (4-(3-bromo-4-(piperidin-4-yloxy)benzyl)- N -(3-(dimethylamino)phenyl)piperazine-1-carboxamide dihydrochloride), a transcriptome-based drug approach. To do this, obtained KR-37524-induced gene expression profile changes in four cell lines (A375, A549, MCF7, and PC3), compared them with...
Methanol dehydrogenase (MDH), an NAD+-dependent oxidoreductase, reversibly converts formaldehyde to methanol. This activity is a key step for both toxic elimination and methanol production in bacterial methylotrophy. We mutated decameric Bacillus methanolicus MDH by directed evolution screened mutants increased reduction Escherichia coli. The mutant with the highest had three amino acid substitutions: F213V, F289L, F356S. To identify individual contributions of these residues activity,...
Background: Fibrinolytic protease from Euphausia superba (EFP) was isolated. Objective: Biochemical distinctions, regulation of the catalytic function, and key residues EFP were investigated. Methods: The serial inhibition kinetic evaluations coupled with measurements fluorescence spectra in presence 4-(2-aminoethyl) benzene sulfonyl fluoride hydrochloride (AEBSF) conducted. computational molecular dynamics (MD) simulations also applied for a comparative study. Results: enzyme behaved as...
Electrophoretic mobility shift assay (EMSA) technology has been widely employed for the analysis of transcription factors such as Forkhead box protein M1 (FOXM1). However, application high-throughput screening (HTS) in performing, analyses are limited it uses time consuming electrophoresis procedure and radioisotopes. In this study, we developed a FOXM1-DNA binding domain (DBD) based on time-resolved fluorescence energy transfer (TR-FRET) that enables HTS inhibitors interaction. This was...
The aim of this study was to characterize the functions mitochondrial creatine kinases in Chinese soft-shelled turtle Pelodiscus sinensis (PSCK-MT1 and PSCK-MT2) function relation hibernation. Computational prediction via molecular dynamics simulations showed that PSCK-MT1 had stronger kinase- creatine-binding affinity than PSCK-MT2. We measured PSCK-MT2 levels myocardium, liver, spleen, lung, kidney, ovary P. before after hibernation found expression these enzymes most significantly...