A5030834931- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Cancer-related gene regulation
- Hybrid Renewable Energy Systems
- Radiomics and Machine Learning in Medical Imaging
- Cancer-related molecular mechanisms research
- Biochemical and Molecular Research
- Biodiesel Production and Applications
- Microencapsulation and Drying Processes
- HIV/AIDS drug development and treatment
- Trace Elements in Health
- Advanced Combustion Engine Technologies
- Heavy Metal Exposure and Toxicity
- Geomagnetism and Paleomagnetism Studies
- Pickering emulsions and particle stabilization
- Photochromic and Fluorescence Chemistry
- Advanced Chemical Physics Studies
- Advanced Cellulose Research Studies
- Chemical Synthesis and Analysis
- Epigenetics and DNA Methylation
- Spectroscopy and Quantum Chemical Studies
- Click Chemistry and Applications
- Enzyme Structure and Function
- Semiconductor materials and devices
Umeå University
2015-2025
University of Zurich
2019-2024
Boston University
2024
Huazhong University of Science and Technology
2024
South China Agricultural University
2020-2023
Beijing Institute of Technology
2022
China North Industries Group Corporation (China)
2019-2022
Henan University of Technology
2022
Harbin Medical University
2021
Second Affiliated Hospital of Harbin Medical University
2021
The methylase METTL3 is the writer enzyme of N6 -methyladenosine (m6 A) modification RNA. Using a structure-based drug discovery approach, we identified inhibitor with potency in biochemical assay 280 nM, while its enantiomer 100 times less active. We observed dose-dependent reduction m6 A methylation level mRNA several cell lines treated already after 16 h treatment, which lasted for at least 6 days. Importantly, prolonged incubation (up to days) did not alter levels other RNA modifications...
•Dynamic structural proteomic screens detect functional changes at high resolution•Detect enzyme activity, phosphorylation, and molecular interactions in situ•Generate new hypotheses increase proteomics coverage•Enabled discovery of a regulatory mechanism glucose uptake E. coli Biological processes are regulated by intermolecular chemical modifications that do not affect protein levels, thus escaping detection classical screens. We demonstrate here global readout based on limited...
Methyltransferase-like 3 (METTL3) and METTL14 form a heterodimeric complex that catalyzes the most abundant internal mRNA modification, N6-methyladenosine (m6A). METTL3 is catalytic subunit binds co-substrate S-adenosyl methionine (SAM), while involved in binding. The m6A modification provides post-transcriptional level control over gene expression as it affects almost all stages of life cycle, including splicing, nuclear export, translation, decay. There increasing evidence for an oncogenic...
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Optogenetic systems using photosensitive proteins and chemically induced dimerization/proximity (CID/CIP) approaches enabled by chemical dimerizers (also termed molecular glues), are powerful tools to elucidate the dynamics of biological dissect complex regulatory networks. Here, we report a versatile chemo‐optogenetic system modular, photoswitchable glues (sMGs) that can undergo repeated cycles optical control switch protein function on off. We use (MD) simulations rationally design sMGs...
Optogenetic systems using photosensitive proteins and chemically induced dimerization/proximity (CID/CIP) approaches enabled by chemical dimerizers (also termed molecular glues), are powerful tools to elucidate the dynamics of biological dissect complex regulatory networks. Here, we report a versatile chemo‐optogenetic system modular, photoswitchable glues (sMGs) that can undergo repeated cycles optical control switch protein function on off. We use (MD) simulations rationally design sMGs...
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 the most popular and successful approaches drug discovery; however, almost all programs protein based. The adaptability RNA world has not been systematically evaluated. This paper describes comprehensive evaluation two widely used protein-based programs—GOLD Glide—for their...
Zr4+ doped α-MnO2 nanowires were successfully synthesized by a hydrothermal method. XRD, SEM, TEM and XPS analyses indicated that Mn3+ ions, Mn4+ Mn4+δ ions co-existed in the crystal structure of nanowires. occupied positions originally belonging to elemental manganese resulted mutual action between ions. The made tend lose their electrons get electrons. Cathodic polarization showed electrocatalytic activity for oxygen reduction reaction (ORR) was remarkably improved doping Zr/Mn molar ratio...
We report 17 small-molecule ligands that compete with N6-methyladenosine (m6A) for binding to the m6A-reader domain of YTHDF2 (YT521-B homology family 2). determined their mode at high resolution by X-ray crystallography and quantified affinity a fluorescence-based assay. 6-Cyclopropyluracil pyrazolopyrimidine derivative have favorable ligand efficiencies 0.47 0.38 kcal mol-1 per non-hydrogen atom, respectively. They represent useful starting points hit optimization.
This study aims to identify inhibitors that bind at the interface of HIV-1 integrase (IN) and human LEDGF/p75, which represents a novel target for anti-HIV therapy. To date, only few such have been reported. Here structure-based virtual screening was performed search from an in-house library natural products their derivatives. Among 38 compounds selected by our strategy, 18 hits were discovered. The two most potent showed IC50 values 0.32 0.26 μM, respectively. Three subsequently assays,...
The 2A proteinase (2Apro) is an enterovirally encoded cysteine protease that plays essential roles in both the processing of viral precursor polyprotein and hijacking host cell translation other processes virus life cycle. Crystallographic studies 2Apro from enterovirus 71 (EV71) its interaction with substrate are reported here. EV71 was comprised N-terminal domain a four-stranded antiparallel β sheet C-terminal six-stranded barrel tightly bound zinc atom. Unlike structures, there open cleft...
N6-Methyladenosine (m6A) is the most frequent modification in eukaryotic messenger RNA (mRNA) and its cellular processing functions are regulated by reader proteins YTHDCs YTHDFs. However, mechanism of m6A recognition still elusive. Here, we investigate this process combining atomistic simulations, site-directed mutagenesis, biophysical experiments using YTHDC1 as a model. We find that N6 methyl group contributes to binding through specific interactions with an aromatic cage (formed Trp377...
Poly(ε-caprolactone) (PCL)-incorporated lignin-chitosan biomass-based nanocomposite porous scaffolds have been effectively prepared by templating oil-in-water Pickering high internal phase emulsions (HIPEs). PCL is dissolved in oil and chitosan lignin nanoparticles originate water. The continuous of the gelled cross-linking with genipin then freeze-dried to obtain scaffolds. resulting display interconnected tunable pore structures. An increase content increases mechanical strength greatly...
The complex of methyltransferase-like proteins 3 and 14 (METTL3-14) is the major enzyme that deposits N6-methyladenosine (m6A) modifications on messenger RNA (mRNA) in humans. METTL3-14 plays key roles various biological processes through its methyltransferase (MTase) activity. However, little known about substrate recognition methyl transfer mechanism from cofactor donor S-adenosylmethionine (SAM). Here, we study MTase by a combined experimental multiscale simulation approach using...
We report a crystallographic analysis of small-molecule ligands the human YTHDC1 domain that recognizes N6-methylated adenine (m6A) in RNA. The 30 binders are fragments (molecular weight < 300 g mol–1) represent 10 different chemotypes identified by virtual screening. Despite structural disorder binding site loop (residues 429–439), most emulate two main interactions −NHCH3 group m6A. These hydrogen bond to backbone carbonyl Ser378 and van der Waals contacts with tryptophan cage. Different...
Abstract In this study, the cinnamon oil (CMO)‐loaded antibacterial composite microcapsules with silicon dioxide (SiO 2 )/poly(melamine formaldehyde) (PMF) hybrid shells are effectively and facilely constructed by in situ polymerization of SiO nanoparticle–stabilized Pickering emulsion templates. The morphological structure, composition, thermal performance determined scanning electronic microscopy, Fourier transform infrared spectroscopy, gravimetric analysis. addition, vitro CMO release...
The catalytic and allosteric mechanisms of insulin receptor kinase (IRK) are investigated by a combination ab initio semiempirical quantum mechanical molecular (QM/MM) methods classical dynamics (MD) simulations. simulations reveal that the reaction proceeds in two steps, starting with transfer proton from substrate Tyr to Asp1132, followed phosphoryl ATP Tyr. enhancement rate IRK upon phosphorylations enzyme's activation loop is found occur mainly via changes free energy landscape step,...
Here we present the development of dCE-2, a structurally novel PROTAC targeting CREB-binding protein (CBP) and E1A-associated (EP300) – two homologous multidomain enzymes crucial for enhancer-mediated transcription. The design dCE-2 was based on crystal structure an in-house bromodomain (BRD) inhibitor featuring as acetyl-lysine mimic 3-methyl cinnoline discovered by high-throughput fragment docking. Our study shows that, despite its modest binding affinity to CBP/EP300-BRD, remarkable...
N6-Methyladenosine (m6A) is the most prevalent chemical modification in human mRNAs. Its recognition by reader proteins enables many cellular functions, including splicing and translation of However, binding mechanisms m6A-containing RNAs to their readers are still elusive due unclear roles m6A-flanking ribonucleotides. Here, we use a model system, YTHDC1 with its RNA motif 5'-G-2G-1(m6A)C+1U+2-3', investigate atomistic simulations, X-ray crystallography, isothermal titration calorimetry....