A5026571067- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Receptor Mechanisms and Signaling
- Radiopharmaceutical Chemistry and Applications
- Psychedelics and Drug Studies
- Crystallization and Solubility Studies
- Pharmacological Receptor Mechanisms and Effects
- X-ray Diffraction in Crystallography
- Nuclear Structure and Function
- Colorectal Cancer Treatments and Studies
- Chemical synthesis and alkaloids
- Neuropeptides and Animal Physiology
- Neurotransmitter Receptor Influence on Behavior
- Biochemical Analysis and Sensing Techniques
- Lung Cancer Treatments and Mutations
- RNA Research and Splicing
- Signaling Pathways in Disease
- Chemical Synthesis and Analysis
- Endoplasmic Reticulum Stress and Disease
- Computational Drug Discovery Methods
- Regulation of Appetite and Obesity
- Protein purification and stability
- Lipid Membrane Structure and Behavior
- Calcium signaling and nucleotide metabolism
- Alkaloids: synthesis and pharmacology
Yonsei University
2013-2025
University of North Carolina at Chapel Hill
2018-2024
Abstract The κ-opioid receptor (KOR) has emerged as an attractive drug target for pain management without addiction, and biased signaling through particular pathways of KOR may be key to maintaining this benefit while minimizing side-effect liabilities. As most G protein-coupled receptors (GPCRs), however, the molecular mechanisms ligand-specific at have remained unclear. To better understand determinants bias, we apply structure determination, atomic-level dynamics (MD) simulations,...
AlphaFold2 (AF2) models have had wide impact but mixed success in retrospective ligand recognition. We prospectively docked large libraries against unrefined AF2 of the σ
Abstract Recent studies show that GPCRs rapidly interconvert between multiple states although our ability to interrogate, monitor and visualize them is limited by a relative lack of suitable tools. We previously reported two nanobodies (Nb39 Nb6) stabilize distinct ligand- efficacy-delimited conformations the kappa opioid receptor. Here, we demonstrate via X-ray crystallography nanobody-targeted allosteric binding site which Nb6 stabilizes ligand-dependent inactive state. As Nb39 an...
Induction of endoplasmic reticulum ( ER )‐to‐Golgi blockade or stress induces Golgi reassembly stacking protein GRASP )‐mediated, Golgi‐independent unconventional cell‐surface trafficking the folding‐deficient ΔF508 ‐cystic fibrosis transmembrane conductance regulator CFTR ). However, molecular mechanisms underlying this process remain elusive. Here, we show that phosphorylation‐dependent dissociation homotypic complexes and subsequent relocalization to play a critical role in secretion ....
Abstract A novel light-driven chloride-pumping rhodopsin (ClR) containing an ‘NTQ motif’ in its putative ion conduction pathway has been discovered and functionally characterized a genomic analysis study of marine bacterium. Here we report the crystal structure ClR from flavobacterium Nonlabens marinus S1-08 T determined under two conditions at 2.0 1.56 Å resolutions. The structures reveal chloride-binding sites, one around protonated Schiff base other on cytoplasmic loop. We identify ‘3...
Abstract AlphaFold2 (AF2) and RosettaFold have greatly expanded the number of structures available for structure-based ligand discovery, even though retrospective studies cast doubt on their direct usefulness that goal. Here, we tested unrefined AF2 models prospectively , comparing experimental hit-rates affinities from large library docking against vs same screens targeting receptors. In σ 2 5-HT2A receptors, struggled to recapitulate ligands had previously found receptors’ structures,...
There is currently a resurgence in exploring the utility of classical psychedelics to treat depression, addiction, anxiety disorders, cluster headaches, and many other neuropsychiatric disorders. A biological target these compounds, hypothesized for their therapeutic actions, 5-HT2A serotonin receptor. Here, we present 7 cryo-EM structures covering all major compound classes psychedelic non-psychedelic agonists, including β-arrestin-biased RS130-180. Identifying molecular interactions...
ABSTRACT Telomeres are essential for chromosome integrity and protection, their maintenance requires the ribonucleoprotein enzyme telomerase. Previously, we have shown that human telomerase reverse transcriptase (hTERT) contains a bipartite nuclear localization signal (NLS; residues 222–240) is responsible import, Akt-mediated phosphorylation of residue S227 important efficient import hTERT. Here, show hTERT binds to importin-α proteins through NLS this heterodimer then forms complex with...
A smoke-derived compound, karrikin (KAR), and an endogenous but as yet unidentified KARRIKIN INSENSITIVE2 (KAI2) ligand (KL) have been identified chemical cues in higher plants that impact on multiple aspects of growth development. Genetic screening light-signaling mutants Arabidopsis thaliana has a mutant designated ply2 (pleiotropic long hypocotyl2) pleiotropic light-response defects. In this study, we used positional cloning to identify the molecular lesion missense mutation...
The EGFR-targeted monoclonal antibodies are a valid therapeutic strategy for patients with metastatic colorectal cancer (mCRC). However, only small subset of mCRC has benefits and there high demands EGFR therapeutics broader patient pool more potent efficacy. In this study, we report GC1118 exhibiting different character in terms binding epitope, affinity, mode action, efficacy from other anti-EGFR antibodies. Structural analysis the EGFR-GC1118 crystal complex revealed that recognizes...
Lysozymes are the first line of defense for a diverse range organisms that catalyze degradation bacterial peptidoglycan. Gram-negative bacteria produce proteinaceous lysozyme inhibitors to protect themselves from action lysozymes. To date, MliC or PliC (membrane-bound periplasmic inhibitor c-type lysozyme, respectively) has been found in various bacteria. Here, we report crystal structures Brucella abortus and its complex with human lysozyme. The structure demonstrates invariant loop...
We report the results of a screen library 925 potential prenyl synthase inhibitors against Trypanosoma brucei farnesyl diphosphate (TbFPPS) and T. brucei, causative agent human African trypanosomiasis. The most potent compounds were lipophilic analogs bone resorption drug zoledronate, some which had submicromolar to low micromolar activity bloodstream form selectivity indices up ∼ 300. evaluated effects two such on survival parasitemia in mouse model infection found that increased by 16...