A5074137044- Chemical Synthesis and Analysis
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Biochemical and Structural Characterization
- Neuropeptides and Animal Physiology
- RNA Interference and Gene Delivery
- Ubiquitin and proteasome pathways
- Nicotinic Acetylcholine Receptors Study
- Erythrocyte Function and Pathophysiology
- RNA and protein synthesis mechanisms
- Plant Stress Responses and Tolerance
- Neuroscience and Neuropharmacology Research
- Advanced biosensing and bioanalysis techniques
- Ion Channels and Receptors
- Monoclonal and Polyclonal Antibodies Research
- Ion Transport and Channel Regulation
- Mycobacterium research and diagnosis
- Plant nutrient uptake and metabolism
- Tuberculosis Research and Epidemiology
- Advanced Polymer Synthesis and Characterization
- Glycosylation and Glycoproteins Research
- Phytochemistry and Biological Activities
- Plant Molecular Biology Research
- Drug Transport and Resistance Mechanisms
- Antimicrobial Peptides and Activities
Hefei National Center for Physical Sciences at Nanoscale
2012-2025
University of Science and Technology of China
2015-2025
Zunyi Medical University
2019-2025
Shandong First Medical University
2023
Center for Life Sciences
2014-2022
Tsinghua University
2014-2022
Hefei University
2014-2020
King Center
2020
High Magnetic Field Laboratory
2014-2016
Chinese Academy of Sciences
2014-2016
Quasi-racemic crystallography has been used to determine the X-ray structures of K27-linked ubiquitin (Ub) chains prepared through total chemical synthesis. Crystal di- and tri-ubiquitins reveal that isopeptide linkages are confined in a unique buried conformation, which provides molecular basis for distinctive function K27 linkage compared other seven Ub chains. triUb were found adopt different structural conformations crystals, one being symmetric whereas triangular. Furthermore,...
Disulfide-rich peptides containing three or more disulfide bonds are promising therapeutic and diagnostic agents, but their preparation is often limited by the tedious low-yielding folding process. We found that a single cystine-to-diaminodiacid replacement could significantly increase efficiency of disulfide-rich thus improve production yields. The practicality this strategy was demonstrated synthesis derivatives μ-conotoxin SIIIA, preclinical hormone hepcidin, trypsin inhibitor EETI-II....
The human calcium-sensing receptor (CaSR) is a class C G protein-coupled (GPCR) responsible for maintaining Ca2+ homeostasis in the blood. general consensus that extracellular principal agonist of CaSR. Aliphatic and aromatic L-amino acids, such as L-Phe L-Trp, increase sensitivity CaSR towards are considered allosteric activators. Crystal structures domain (ECD) dimer have demonstrated L-Trp binding sites conformational changes ECD upon Ca2+/L-Trp binding. However, it remains to be...
Racemic or quasi-racemic crystallography recently emerges as a useful technology for solution of the crystal structures biomacromolecules. It remains unclear to what extent biomacromolecules opposite handedness can differ from each other in racemic crystallography. Here we report finding that monomeric d-ubiquitin (Ub) has propensity cocrystallize with different dimers, trimers, and even tetramer l-Ub. In these cocrystals unconnected d-Ubs self-assemble form pseudomirror images oligomers...
Acid-sensing ion channels (ASICs) are proton-gated cation that involved in diverse neuronal processes including pain sensing. The peptide toxin Mambalgin1 (Mamba1) from black mamba snake venom can reversibly inhibit the conductance of ASICs, causing an analgesic effect. However, detailed mechanism by which Mamba1 inhibits ASIC1s, especially how binding to extracellular domain affects conformational changes transmembrane ASICs remains elusive. Here, we present single-particle cryo-EM...
The β2-adrenergic receptor (β2AR) is a G-protein-coupled (GPCR) that responds to the hormone adrenaline and an important drug target in context of respiratory diseases, including asthma. β2AR function can be regulated by post-translational modifications such as phosphorylation ubiquitination at C-terminus, but access full-length with well-defined homogeneous modification patterns critical for biochemical biophysical studies remains challenging. Here, we report practical synthesis...
Sortase A (SrtA)-mediated ligation, a popular method for protein labeling and semi-synthesis, is limited by its reversibility dependence on the LPxTG motif, where "x" any amino acid. Here, we report that SrtA can mediate efficient irreversible ligation of protein/peptide containing C-terminal thioester with another bearing an N-terminal Gly, broad tolerance wide variety LPxT-derived sequences. This strategy, thioester-assisted SrtA-mediated enabled expedient preparation proteins various N-...
The endogenous cyclic tetradecapeptide SST14 was reported to stimulate all five somatostatin receptors (SSTR1-5) for hormone release, neurotransmission, cell growth arrest and cancer suppression. Two SST14-derived short SST analogues (lanreotide or octreotide) with improved stability longer lifetime were developed as drugs preferentially activate SSTR2 treat acromegalia neuroendocrine tumors. Here, cryo-EM structures of the human SSTR2-Gi complex bound SST14, octreotide lanreotide determined...
Increasing the expression of ATP-binding cassette transporter A1 (ABCA1) can lower cellular cholesterol levels and prevent foam cell formation. In this study, a series 5, 6-dihydro-8H-isoquinolino[1, 2-b]quinazolin-8-one derivatives were synthesised assessed for their ability to up-regulate ABCA1 expression. The structure-activity relationship was explored summarised. Among 28 derivatives, compound 3 exhibited most potent activity in activating promoter (2.50-fold), significantly...
Abstract Biased allosteric modulators (BAMs) of G protein-coupled receptors (GPCRs) have been at the forefront drug discovery owing to their potential selectively stimulate therapeutically relevant signaling and avoid on-target side effects. Although structures GPCRs in complex with protein or GRK a BAM-bound state recently resolved, revealing that BAM can induce biased by directly modulating interactions between these two transducers, no GPCR–arrestin structure has yet determined, limiting...
An efficient one-pot chemical synthesis of snake venom toxin Mambalgin-1 was achieved using an azide-switch strategy combined with hydrazide-based native ligation.
Glioblastoma multiforme (GBM) is a WHO grade 4 glioma and the most common malignant primary brain tumor. Addressing clinical management of GBM presents an exceptionally daunting intricate challenge, particularly in overcoming blood–brain barrier (BBB) to deliver effective therapies brain. Nanotechnology-based drug delivery systems have exhibited considerable promise tackling this aggressive cancer. However, BBB remains key challenge achieving nanocarriers. Here, we optimized lipid...
In this study, a series of 1, 4-benzodioxan-substituted thienyl chalcone derivatives were designed, synthesized and evaluated for their inhibitory activities against human MAO-B (hMAO-B). The structure-activity relationship was investigated summarized. Among the 22 derivatives, compound 12 showed most potent activity, which exhibited an IC50 0.11 µM with selectivity index greater than 333. Kinetics reversibility studies confirmed that acted as competitive reversible inhibitor hMAO-B....
Our skin safeguards the body homeostasis for health and also provides psychological consolation in social life. Natural essential oils are widely used maintenance, while molecular target mechanism of action remain largely unknown. Here, we report that citronellal, a plant-derived acyclic monoterpene commonly personal care, stimulates renewal by promoting keratinocyte proliferation through activation TRPV3. We further present cryo-EM structures human TRPV3 complex with monoterpenes, including...
Post-translational modifications (e.g., ubiquitylation) of histones play important roles in dynamic regulation chromatin. Histone ubiquitylation has been speculated to directly influence the structure and dynamics nucleosomes. However, structural information for ubiquitylated nucleosomes is still lacking. Here we report an alternative strategy total chemical synthesis homogenous histone H2B-K34-ubiquitylation (H2B-K34Ub) by using acid-cleavable auxiliary-mediated ligation peptide hydrazides...
Acid-sensing ion channels (ASICs) are neuronal voltage-independent Na+ that activated by extracellular acidification. ASICs play essential roles in a wide range of physiological processes, including sodium homeostasis, synaptic plasticity, neurodegeneration, and sensory transduction. Mambalgins, family three-finger toxins isolated from black mamba venom, specifically inhibit to exert strong analgesic effects vivo, thus thought have potential therapeutic values against pain. However, the...
Mutations in genes encoding PINK1 (PTEN-induced kinase 1) and Parkin (E3 ubiquitin ligase) are identified familial Parkinson’s disease. However, it remains unclear whether the phosphorylated Ub ...
Histone ubiquitylation and deubiquitylation processes the mechanisms of their regulation are closely relevant to field epigenetics. Recently, deubiquitylating enzyme USP51 was reported selectively cleave on histone H2A at K13 or K15 (i.e., H2AK13Ub H2AK15Ub), but not K119 H2AK119Ub), in nucleosomes vivo. To elucidate mechanism for selectivity USP51, we constructed structurally well-defined vitro protein systems with a ubiquitin modification precise sites. A total chemical synthesis procedure...