Xianqiang Sun

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Allosteric sodium in the helix bundle of a G protein-coupled receptor (GPCR) can modulate the receptor activation on the intracellular side. This phenomenon has confounded the GPCR community for decades. In this work, we present a theoretical model that reveals the mechanism of the allosteric modulation induced by sodium in the δ-opioid receptor. We found(More)
Integration of viral-DNA into host chromosome mediated by the viral protein HIV-1 integrase (IN) is an essential step in the HIV-1 life cycle. In this process, human protein Lens epithelium-derived growth factor (LEDGF/p75) is discovered to function as a cellular co-factor for integration. LEDGF/p75-HIV-1 IN interaction represents an attractive target for(More)
The immune checkpoint receptor PD-1 and its ligand, PD-L1, have emerged as key regulators of anti-tumor immunity in humans. Recently, we reported an ultra-high-affinity PD-1 mutant, termed high-affinity consensus (HAC) PD-1, which shows superior therapeutic efficacy in mice compared with antibodies. However, the molecular details underlying the action of(More)
The aim of this study is to explore the potential enhancing effect of ginsenoside 20(S)-Rh2 (Rh2) towards ciprofloxacin (CIP) against Staphylococcus aureus (S. aureus) infection in vitro and in vivo, and analyze the possible mechanisms through NorA inhibition from a target cellular pharmacokinetic view. In combination with non-toxic dosage of Rh2, the(More)
The corticotropin releasing factors receptor-1 and receptor-2 (CRF1R and CRF2R) are therapeutic targets for treating neurological diseases. Antagonists targeting CRF1R have been developed for the potential treatment of anxiety disorders and alcohol addiction. It has been found that antagonists targeting CRF1R always show high selectivity, although CRF1R and(More)
The κ opioid receptor (κOR) is a member of G-protein-coupled receptors, and is considered as a promising drug target for treating neurological diseases. κOR selective 6'-GNTI was proved to be a G-protein biased agonist, whereas 5'-GNTI acts as an antagonist. To investigate the molecular mechanism of how these two ligands induce different behaviors of the(More)
Neomorphic mutation R140Q in the metabolic enzyme isocitrate dehydrogenase 2 (IDH2) is found to be a driver mutation in cancers. Recent studies revealed that allosteric inhibitors could selectively inhibit IDH2/R140Q and induce differentiation of TF-1 erythroleukemia and primary human AML cells. However, the allosteric inhibition mechanism is not very(More)
By using of structure-based virtual screening, 13 novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors were discovered from 197,116 compounds in the SPECS database here. Among them, 8 compounds significantly inhibited EGFR kinase activity with IC(50) values lower than 10 μM.(More)
G-protein-coupled receptors (GPCRs) are integral membrane proteins that mediate cellular response to an extensive variety of extracellular stimuli. Studies of rhodopsin, a prototype GPCR, have suggested that water plays an important role in mediating the activation of family A GPCRs. However, our understanding of the function of water molecules in the GPCR(More)
Ribonucleic acid (RNA) molecules play central roles in a variety of biological processes and, hence, are attractive targets for therapeutic intervention. In recent years, molecular docking techniques have become one of the most popular and successful approaches in drug discovery; however, almost all docking programs are protein based. The adaptability of(More)