A5002337846- Protease and Inhibitor Mechanisms
- Renin-Angiotensin System Studies
- Protein Interaction Studies and Fluorescence Analysis
- Blood Coagulation and Thrombosis Mechanisms
- Hormonal and reproductive studies
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Antibiotic Resistance in Bacteria
- TGF-β signaling in diseases
- Bone Metabolism and Diseases
- Rheumatoid Arthritis Research and Therapies
- Signaling Pathways in Disease
- Hypothalamic control of reproductive hormones
- Calcium signaling and nucleotide metabolism
- Sirtuins and Resveratrol in Medicine
- Cancer-related molecular mechanisms research
- Calpain Protease Function and Regulation
- Hormonal Regulation and Hypertension
- Congenital heart defects research
- NF-κB Signaling Pathways
- Folate and B Vitamins Research
- Pharmacological Effects of Medicinal Plants
- Enzyme function and inhibition
- PARP inhibition in cancer therapy
- Bone and Dental Protein Studies
- Pregnancy and preeclampsia studies
Shanghai Jiao Tong University
2015-2024
Guangzhou University of Chinese Medicine
2017-2020
First Affiliated Hospital of Guangzhou University of Chinese Medicine
2018
Tongren Hospital
2016
Addenbrooke's Hospital
2014-2015
University of Cambridge
2006-2015
University of Göttingen
2010
Max Planck Institute of Biochemistry
2006
The hormones that most directly control tissue activities in health and disease are delivered by two noninhibitory members of the serpin family protease inhibitors, thyroxine-binding globulin (TBG) corticosteroid-binding globulin. structure TBG bound to tetra-iodo thyroxine, solved here at 2.8 Å, shows how thyroxine is carried a surface pocket on molecule. This unexpected binding site confirmed mutations associated with loss hormone both also homologously strikingly differs from other...
Multidrug-resistant (MDR) organisms have increased worldwide, posing a major challenge for the clinical management of infection. Bacteriophage is expected as potential effective therapeutic agents difficult-to-treat infections. When performing bacteriophage therapy, susceptibility lytic to target bacteria selected by laboratory isolate from patients. The presence subpopulation in main population tested cells, coupled with rapid development phage-resistant populations, will make therapy...
The Klebsiella pneumoniae (K. pneumoniae, Kp) populations carrying both resistance-encoding and virulence-encoding mobile genetic elements (MGEs) significantly threaten global health. In this study, we identified a new anti-CRISPR gene (acrIE10) on conjugative plasmid with self-target sequence in K. type I-E* CRISPR-Cas system. AcrIE10 interacts the Cas7* subunit of crystal structure AcrIE10-KpCas7* complex suggests that suppresses by binding directly to Cas7 prevent its hexamerization,...
Corticosteroids are transported in the blood by a serpin, corticosteroid-binding globulin (CBG), and their normally equilibrated release can be further triggered cleavage of reactive loop CBG. We report here crystal structures cleaved human CBG (cCBG) at 1.8-Å resolution its complex with cortisol 2.3-Å resolution. As expected, on cleavage, undergoes irreversible S-to-R serpin transition, loops being fully incorporated into central β-sheet. A connecting helix D, which is helix-like...
The release of hormones from thyroxine-binding globulin (TBG) and corticosteroid-binding (CBG) is regulated by movement the reactive center loop in out β-sheet A molecule. To investigate how these changes are transmitted to hormone-binding site, we developed a sensitive assay using synthesized thyroxine fluorophore solved crystal structures cleaved TBG together with its complexes thyroxine, fluorophores, furosemide, mefenamic acid. Cleavage results complete insertion into substantial but...
BMP9, a member of the TGFβ superfamily, is homodimer that forms signaling complex with two type I and II receptors. Signaling through high-affinity activin receptor-like kinase 1 (ALK1) in endothelial cells, circulating BMP9 acts as vascular quiescence factor, maintaining homeostasis. also most potent BMP for inducing osteogenic mesenchymal stem cells vitro promoting bone formation vivo. This activity requires ALK1, lower affinity receptor ALK2, higher concentrations BMP9. In adults,...
The Z mutation (E342K) of α1-antitrypsin (α1-AT), carried by 4% Northern Europeans, predisposes to early onset emphysema due decreased functional α1-AT in the lung and liver cirrhosis accumulation polymers hepatocytes. However, it remains unclear why causes intracellular polymerization nascent 15% expressed is secreted into circulation as functional, but polymerogenic, monomers. Here, we solve crystal structure Z-monomer have engineered replacements assess conformational role residue Glu-342...
The sirtuin enzyme family members, SIRT1 and SIRT2, play both tumor-promoting tumor-suppressing roles, depending on the context experimental conditions. Compounds that inhibit either or SIRT2 show promising antitumor effects in several types of cancer models, vitro vivo. simultaneous inhibition is helpful treating by completely blocking p53 deacetylation, leading to cell death. However, only a few SIRT1/2 dual inhibitors have been developed. Here, we report discovery novel series via...
BackgroundPsoriasis is a common chronic inflammatory skin disease which lacks effective strategies for the treatment. Natural compounds with biological activities are good tools to identify new targets therapeutic potentials. Acetyl-11-keto-β-boswellic acid (AKBA) most bioactive ingredient of boswellic acids, group anti-inflammatory and anti-cancer properties. Target identification AKBA metabolomics analysis psoriasis helped elucidate molecular mechanism underlying its effect, provide...
Osteolytic skeletal disorders are caused by an imbalance in the osteoclast and osteoblast function. Suppressing differentiation resorptive function of is a key strategy for treating osteolytic diseases. Dracorhodin perchlorate (D.P), active component from dragon blood resin, has been used facilitating wound healing anti-cancer treatments. In this study, we determined effect D.P on We have found that inhibited RANKL-induced formation resorbed pits hydroxyapatite-coated plate dose-dependent...
Kallistatin, also known as SERPINA4, has been implicated in the regulation of blood pressure and angiogenesis, due to its specific inhibition tissue kallikrein 1 (KLK1) and/or by heparin binding ability. The on kallistatin shown block KLK1 but detailed molecular mechanism underlying this blockade is unclear. Here we solved crystal structures human complex with at 1.9 1.8 Å resolution, respectively. show that a conserved serpin fold undergoes typical stressed-to-relaxed conformational changes...
Plasminogen activator inhibitor-1 (PAI-1) is a member of the serpin (serine protease inhibitor) superfamily. Like most serpins, inhibitory function PAI-1 relies on flexible reactive centre loop (RCL) undertaking striking conformational transition. We have investigated dynamics RCL by time-resolved fluorescence anisotropy. A heterogeneous population model with three rotational correlation times has been employed to account for "dip and rise" observed in anisotropy decay curves. The becomes...
Influenza viruses often pose a serious threat to animals and human health. In an attempt explore the potential of herbal medicine as treatment for influenza virus infection, eleutheroside B1, coumarin compound extracted from herba sarcandrae, was identified, which exhibited antiviral anti‑inflammatory activities against A virus. this study, high‑throughput RNA sequencing isobaric tags relative absolute quantification (iTRAQ) assays were performed determine alterations in non‑coding (ncRNA)...
Kallistatin is a serine protease inhibitor (serpin) which specifically inhibits human tissue kallikrein; however, its inhibitory activity inhibited by heparin. In order to elucidate the underlying mechanism, recombinant kallistatin was prepared in Escherichia coli and protein crystallized sitting-drop vapour-diffusion method. X-ray diffraction data were collected 1.9 Å resolution. The crystals found belong space group P 6 1 , with unit-cell parameters = 113.51, b c 76.17 Å. Initial analysis...
The LKB1 tumor suppressor kinase regulates activity of the AMPK family kinases.LKB1 is activaty regulated by pseudokinase STRADa and scaffolding protein MO25a through an unknown, phosphorylation-independent, mechanism.Here we describe 2.65 Å structure heterotrimeric LKB1/STRADa/MO25a complex, revealing unusual allosteric mechanism activation.STRADa adopts a closed conformation typical active kinases, binds as pseudosubstrate.STRADa binding, promotes LKB1, which further stabilized interacting...