A5103243937- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Cannabis and Cannabinoid Research
- Hedgehog Signaling Pathway Studies
- Photochromic and Fluorescence Chemistry
- Monoclonal and Polyclonal Antibodies Research
- Neuroscience and Neuropharmacology Research
- Berberine and alkaloids research
- Computational Drug Discovery Methods
- Cell Adhesion Molecules Research
- Axon Guidance and Neuronal Signaling
- Mass Spectrometry Techniques and Applications
- Neurotransmitter Receptor Influence on Behavior
- GABA and Rice Research
- T-cell and B-cell Immunology
- Genetics and Neurodevelopmental Disorders
- Bacterial biofilms and quorum sensing
- Chemical Synthesis and Analysis
- Marine Toxins and Detection Methods
- Glycosylation and Glycoproteins Research
- Fibroblast Growth Factor Research
- Protein Kinase Regulation and GTPase Signaling
- Microbial Fuel Cells and Bioremediation
- Pharmacological Effects and Assays
- Chemokine receptors and signaling
ShanghaiTech University
2019-2022
Stony Brook University
2012
Eli Lilly (United States)
2005
Although several reports have documented nitric oxide (NO) regulation of biofilm formation, the molecular basis this phenomenon is unknown. In many bacteria, an H-NOX (heme-nitric oxide/oxygen-binding) gene found near a diguanylate cyclase (DGC) gene. domains are conserved hemoproteins that known NO sensors. It widely recognized cyclic di-GMP (c-di-GMP) ubiquitous bacterial signaling molecule regulates transition between motility and biofilm. Therefore, may influence formation through DGC,...
Phytocannabinoids, such as the principal bioactive component of marijuana, Δ 9 -tetrahydrocannabinol, have been used for thousands years medical and recreational purposes. -Tetrahydrocannabinol endogenous cannabinoids (e.g., anandamide) initiate their agonist properties by stimulating cannabinoid family G protein-coupled receptors (CB 1 CB 2 ). The biosynthesis physiology anandamide is well understood, but its mechanism uptake (resulting in signal termination fatty acid amide hydrolase) has...
Adrenergic receptors are highly homologous while at the same time display a wide diversity of ligand and G-protein binding, understanding this is key for designing selective or biased drugs them. Here, we determine two crystal structures α2A adrenergic receptor (α2AAR) in complex with partial agonist an antagonist. Key non-conserved residues from ligand-binding pocket (Phe7.39 Tyr6.55) to coupling region (Ile34.51 Lys34.56) discovered play role interplay between agonism signaling α2AAR,...
Subtype selectivity and functional bias are vital in current drug discovery for G protein-coupled receptors (GPCRs) as selective biased ligands expected to yield leads with optimal on-target benefits minimal side-effects. However, structure-based design medicinal chemistry exploration remain challenging part because of highly conserved binding pockets within subfamilies. Herein, we present an affinity mass spectrometry approach screening herbal extracts identify active a GPCR, the 5-HT2C...
Abstract Muscarinic acetylcholine receptors (mAChRs) respond to the neurotransmitter and play important roles in human nervous system. receptor 4 (M4R) is a promising drug target for treating neurological mental disorders, such as Alzheimer’s disease schizophrenia. However, lack of understanding on M4R’s activation by subtype selective agonists hinders its therapeutic applications. Here, we report structural characterization M4R allosteric agonist, compound-110, well agonist iperoxo positive...
Highlights•Crystal structure of human α2CAR in complex with RS79948 is solved•A specific loosened helix at the top TM4 involved receptor activation•Extracellular regions play a role determining α2 adrenergic subtype selectivitySummaryAdrenergic G-protein-coupled receptors (GPCRs) mediate different cellular signaling pathways presence endogenous catecholamines and important roles both physiological pathological conditions. Extensive studies have been carried out to investigate function β...
Inspired by recent progress in structural studies of the smoothened receptor (SMO), a group affinity probes were developed to specifically light up SMO grafting small fluorescent at specific residue K395.
Human muscarinic receptor M4 belongs to the class A subfamily of G-protein-coupled receptors (GPCRs). has emerged as an attractive drug target for treatment Alzheimer's disease and schizophrenia. Recent results showed that M4-mediated cholinergic transmission is related motor symptoms in Parkinson's disease. Selective ligand design five acetylcholine (mAchR) subtypes currently remains challenging owing high sequence structural similarity their orthosteric binding pockets. In order obtain...
Azobenzene-embedded photoswitchable ligands are the widely used chemical tools in photopharmacological studies. Current approaches to azobenzene introduction rely mainly on isosteric replacement of typical azologable groups. However, atypical scaffolds may offer more opportunities for photoswitch remodeling, which chemically an overwhelming majority. Herein, we investigate rational remodeling introduction, as exemplified development cannabinoid receptor 2 (CB2). Based analysis residue-type...
Class F G protein-coupled receptors are characterized by a large extracellular domain (ECD) in addition to the common transmembrane (TMD) with seven α-helixes. For smoothened receptor (SMO), structural studies revealed dissected ECD and TMD, their integrated assemblies. However, distinct assemblies were reported under different circumstances. Using an unbiased approach based on four series of cross-conjugated bitopic ligands, we explore relationship between active status assembly. Different...
An underside binding site was recently identified in the transmembrane domain of smoothened receptor (SMO). Herein, we report efforts exploration new insights into interactions between ligand and SMO. The hydantoin core middle parent compound found to be highly conservative chirality, ring size, substituents. On each benzene at two ends, a plethora variations, particularly halogen substitutions, were introduced investigated. Analysis structure-activity relationship revealed miscellaneous...