A5050074262- Cancer, Hypoxia, and Metabolism
- Microbial Natural Products and Biosynthesis
- RNA and protein synthesis mechanisms
- Metabolism, Diabetes, and Cancer
- Fibroblast Growth Factor Research
- Plant biochemistry and biosynthesis
- Enzyme Production and Characterization
- Protein Structure and Dynamics
- CRISPR and Genetic Engineering
- Genomics and Phylogenetic Studies
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- Seaweed-derived Bioactive Compounds
- Peptidase Inhibition and Analysis
- CAR-T cell therapy research
- Adipose Tissue and Metabolism
- Protein Degradation and Inhibitors
- Glycosylation and Glycoproteins Research
- Electron Spin Resonance Studies
- Cancer-related Molecular Pathways
- Renal cell carcinoma treatment
- Natural product bioactivities and synthesis
- Biochemical and Structural Characterization
Shandong University
2019-2025
State Key Laboratory of Microbial Technology
2019-2025
Qingdao University
2019
The aryl hydrocarbon receptor (AHR) possesses an extraordinary capacity to sense and respond a wide range of small-molecule ligands, ranging from polycyclic aromatic hydrocarbons endogenous compounds. Upon ligand binding, AHR translocates the cytoplasm nucleus, forming transcriptionally active complex with nuclear translocator (ARNT), for DNA binding initiation gene expression programs that include cellular detoxification pathways immune responses. Here, we examine molecular mechanisms...
Abstract Overexpressed pro-survival B-cell lymphoma-2 (BCL-2) family proteins BCL-2 and BCL-X L can render tumor cells malignant. Leukemia drug venetoclax is currently the only approved selective inhibitor. However, its application has led to an emergence of resistant mutations, calling for drugs with innovative mechanism action. Herein we present cyclic peptides (CPs) nanomolar-level binding affinities or , further reveal structural functional mechanisms how these CPs target two in a...
Abstract Nonribosomal peptide synthetases containing starter condensation domains direct the biosynthesis of nonribosomal lipopeptides, which generally exhibit wide bioactivities. The acyl chain has strong impacts on bioactivity and toxicity, but lack an in-depth understanding domain-mediated lipoinitiation limits bioengineering NRPSs to obtain novel derivatives with desired chains. Here, we show that chains lipopeptides rhizomide, holrhizin, glidobactin were modified by engineering domain,...
Abstract Hypoxia-inducible factors (HIFs) are α/β heterodimeric transcription modulating cellular responses to the low oxygen condition. Among three HIF-α isoforms, HIF-3α is least studied date. Here we show that oleoylethanolamide (OEA), a physiological lipid known regulate food intake and metabolism, binds selectively HIF-3α. Through crystallographic analysis of HIF-3 heterodimer in both apo OEA-bound forms, hydrogen-deuterium exchange mass spectrometry (HDX-MS), molecular dynamics (MD)...
The limited efficiency of the available tools for genetic manipulation Pseudomonas limits fundamental research and utilization this genus. We explored properties a lambda Red-like operon (BAS) from aeruginosa phage Ab31 Rac bacteriophage RecET-like (RecTEPsy) syringae pv. B728a. Compared with RecTEPsy, BAS was functional at higher temperature indicating potential to be generic system Pseudomonas. Owing lack RecBCD inhibitor in operon, we added Redγ or Pluγ found increased recombineering...
Neuronal PER-ARNT-SIM (PAS) domain protein 4 (NPAS4) is a protective transcriptional regulator whose dysfunction has been linked to variety of neuropsychiatric and metabolic diseases. As member the basic helix–loop–helix (bHLH-PAS) transcription factor family, NPAS4 distinguished by an ability form functional heterodimers with aryl hydrocarbon receptor nuclear translocator (ARNT) ARNT2, both which are also bHLH-PAS family members. Here, we describe quaternary architectures NPAS4-ARNT...
Hypoxia-inducible factor (HIF)-2<i>α</i> and its obligate heterodimerization partner aryl hydrocarbon receptor nuclear translocator (ARNT), are both members of the basic helix-loop-helix-PER-ARNT-SIM transcription family. Previous studies have identified HIF-2<i>α</i> as a key oncogenic driver in clear cell renal carcinoma (ccRCC), rendering it promising drug target for this type kidney cancer. Belzutifan is first inhibitor approved treating ccRCC other cancers associated with von...
Abstract Glycosyltransferases typically display acceptor substrate flexibility but more stringent donor specificity. BsGT-1 is a highly effective glycosyltransferase to glycosylate macrolides, including epothilones, promising antitumor compounds. Here, we show that has three major regions significantly influencing the glycodiversification of epothilone B based on structural molecular docking, “hot spots” alanine scanning, and site saturation mutagenesis. Mutations in PSPG-like motif region...
Hypoxia-inducible factor-2 (HIF-2) is a heterodimeric transcription factor formed through dimerization between an oxygen-sensitive subunit HIF-2α and its obligate partner ARNT. Enhanced HIF-2 activity drives some cancers, while reduced causes anemia in chronic kidney disease. Therefore, modulation of via direct-binding ligands could provide many new therapeutic benefits. Here, we explored chemical using combined crystallographic, biophysical, cell-based functional studies. We found...