A5085180521- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Ubiquitin and proteasome pathways
- Bladder and Urothelial Cancer Treatments
- MicroRNA in disease regulation
- Cancer Immunotherapy and Biomarkers
- Circular RNAs in diseases
- Peptidase Inhibition and Analysis
- RNA and protein synthesis mechanisms
- Ferroptosis and cancer prognosis
- Urinary and Genital Oncology Studies
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Computational Drug Discovery Methods
- Polyamine Metabolism and Applications
- Hepatocellular Carcinoma Treatment and Prognosis
- Histone Deacetylase Inhibitors Research
- Cancer, Hypoxia, and Metabolism
- Extracellular vesicles in disease
- Colorectal Cancer Screening and Detection
- Neuroendocrine Tumor Research Advances
- RNA Research and Splicing
Structural Genomics Consortium
2015-2025
Sun Yat-sen Memorial Hospital
2016-2025
Sun Yat-sen University
2016-2025
University of Toronto
2015-2025
Huazhong University of Science and Technology
2016-2024
Tongji Hospital
2016-2024
First Affiliated Hospital of Jiangxi Medical College
2022-2024
Jiangxi Provincial People's Hospital
2018-2024
Second Affiliated Hospital of Nanchang University
2022-2024
Nanchang University
2021-2024
Protein arginine methyltransferases (PRMTs) play a crucial role in variety of biological processes. Overexpression PRMTs has been implicated various human diseases including cancer. Consequently, selective small-molecule inhibitors have pursued by both academia and the pharmaceutical industry as chemical tools for testing therapeutic hypotheses. are divided into three categories: type I which catalyze mono- asymmetric dimethylation residues, II symmetric III PRMT catalyzes only...
SET domain methyltransferases deposit methyl marks on specific histone tail lysine residues and play a major role in epigenetic regulation of gene transcription. We solved the structures catalytic domains GLP, G9a, Suv39H2 PRDM2, four eight known human H3K9 their apo conformation or complex with donating cofactor, peptide substrates. analyzed structural determinants for methylation state specificity, designed G9a mutant able to tri-methylate H3K9. show that I-SET acts as rigid docking...
Skin tissue, composed of epidermis, dermis, and subcutaneous is the largest organ human body.It serves as a protective barrier against pathogens physical trauma plays crucial role in maintaining homeostasis.Skin diseases, such psoriasis, dermatitis, vitiligo, are prevalent can seriously impact quality patient life.Exosomes lipid bilayer vesicles derived from multiple cells with conserved biomarkers important mediators intercellular communication.Exosomes skin cells, blood, stem main types...
Increasing evidence has suggested that dysregulation of certain microRNAs (miRNAs) may contribute to tumorigenesis. microRNA-125b (miR-125b) was implicated have close relationship with cell proliferation and differentiation, downregulation miR-125b observed in various types cancers. However, the biological function bladder tumorigenesis is still unknown. In our study, we showed expression significantly decreased cancer tissues four lines. Moreover, could suppress cells form colonies vitro...
Significance Protein methyltransferases constitute an emerging but undercharacterized class of therapeutic targets with diverse roles in normal human biology and disease. Small-molecule “chemical probes” can be powerful tools for the functional characterization such enzymes, here we report discovery ( R )-PFI-2—a first-in-class, potent, highly selective, cell-active inhibitor methyltransferase activity SETD7 [SET domain containing (lysine methyltransferase) 7]—and two related compounds...
Background The PWWP domain was first identified as a structural motif of 100–130 amino acids in the WHSC1 protein and predicted to be protein-protein interaction domain. It belongs Tudor 'Royal Family', which consists Tudor, chromodomain, MBT domains. While chromodomain domains have long been known bind methylated histones, shown exhibit histone binding ability only until recently. Methodology/Principal Findings has DNA domain, but sequence analysis previous studies show that exhibits...
CD8(+) TILs at different tumor sites have diverse clinical attributes, which might result from distinct microenvironments that promote differentiation into subsets. However, only a few markers been identified can define T-cell CD103 is marker of tissue resident memory T cells. In this retrospective study we investigated the cellular source and significance expression in urothelial cell carcinoma bladder tissues situ.Immunohistochemistry immunofluorescence were used to identify tissues....
Epigenetic regulation is involved in numerous physiological and pathogenic processes. Among the key regulators that orchestrate epigenetic signaling are over 50 human protein lysine methyltransferases (PKMTs). Interrogation of functions individual PKMTs can be facilitated by target-specific PKMT inhibitors. Given emerging need for such small molecules, we envisioned an approach to identify methyltransferase inhibitors screening privileged small-molecule scaffolds against diverse...
Polycomb repressive complex 2 (PRC2) is an important regulator of cellular differentiation and cell type identity. Overexpression or activating mutations EZH2, the catalytic component PRC2 complex, are linked to hyper-trimethylation lysine 27 histone H3 (H3K27me3) in many cancers. Potent EZH2 inhibitors that reduce levels H3K27me3 kill mutant lymphoma cells efficacious a mouse xenograft model malignant rhabdoid tumors. Unlike most SET domain methyltransferases, requires components, SUZ12...
// Kazuhide Nakayama 1, * , Magdalena M. Szewczyk 2, Carlo dela Sena Hong Wu 2 Aiping Dong Zeng Fengling Li Renato Ferreira de Freitas Mohammad S. Eram Matthieu Schapira 3 Yuji Baba 1 Mihoko Kunitomo Douglas R. Cary Michiko Tawada 4 Akihiro Ohashi Yasuhiro Imaeda Kumar Singh Saikatendu 5 Charles E. Grimshaw 6 Masoud Vedadi Cheryl H. Arrowsmith 7 Dalia Barsyte-Lovejoy Atsushi Kiba Daisuke Tomita and Peter J. Brown Oncology Drug Discovery Unit, Pharmaceutical Research Division, Takeda Company...
Epstein-Barr virus-associated gastric cancer (EBVaGC) shows a robust response to immune checkpoint inhibitors. Therefore, cost-efficient and accessible tool is needed for discriminating EBV status in patients with cancer. Here we introduce deep convolutional neural network called EBVNet its fusion pathologists predicting EBVaGC from histopathology. The yields an averaged area under the receiver operating curve (AUROC) of 0.969 internal cross validation, AUROC 0.941 on external dataset...
The crystal structures of two ternary complexes human spermine synthase (EC 2.5.1.22), one with 5′-methylthioadenosine and spermidine the other spermine, have been solved. They show that enzyme is a dimer identical subunits. Each monomer has three domains: C-terminal domain, which contains active site similar in structure to synthase; central domain made up four β-strands; an N-terminal remarkable structural similarity S-adenosylmethionine decarboxylase, forms aminopropyl donor substrate....
Aminopropyltransferases transfer aminopropyl groups from decarboxylated S-adenosylmethionine to amine acceptors, forming polyamines. Structural and biochemical studies have been carried out with the human spermidine synthase, which is highly specific for putrescine as acceptor, Thermotoga maritima prefers but more tolerant of other substrates. Comparison structures synthase both substrates products known structure T. complexed a multisubstrate analogue inhibitor analysis properties...
Significance Many proteins undergo various posttranslational modifications for proper functions. One such modification is methylation carried out by enzyme–cofactor pairs of protein methyltransferases (PMTs) and S -adenosyl- L -methionine (SAM). Identification methylated quite challenging because the small size chemical inertness methyl group. To address this challenge, we have synthesized SAM surrogates replacing SAM’s group with bulky, chemically active functionalities demonstrated their...
G9a-like protein (GLP) and G9a are highly homologous lysine methyltransferases (PKMTs) sharing approximately 80% sequence identity in their catalytic domains. GLP form a heterodimer complex catalyze mono- dimethylation of histone H3 9 nonhistone substrates. Although they closely related, possess distinct physiological pathophysiological functions. Thus, or selective small-molecule inhibitors useful tools to dissect biological We previously reported potent G9a/GLP dual including UNC0638...
Accurate pathological diagnosis of invasion depth and histologic grade is key for clinical management in patients with bladder cancer (BCa), but it labour-intensive, experience-dependent subject to interobserver variability. Here, we aimed develop a artificial intelligence diagnostic model (PAIDM) BCa diagnosis.A total 854 whole slide images (WSIs) from 692 were included divided into training validation sets. The PAIDM was developed using the set based on deep learning algorithm ScanNet,...
The CACHE challenges are a series of prospective benchmarking exercises to evaluate progress in the field computational hit-finding. Here we report results inaugural challenge which 23 teams each selected up 100 commercially available compounds that they predicted would bind WDR domain Parkinson's disease target LRRK2, with no known ligand and only an apo structure PDB. lack binding data presumably low druggability is hit finding methods. Of 1955 molecules by participants Round 1 challenge,...
Histone acetyltransferase 1 is the founding member of histone superfamily and catalyzes lysine acetylation newly synthesized H4. Here we report a 1.9-Å resolution crystal structure human in complex with acetyl coenzyme A H4 peptide. The reveals that cofactor side chain 12 peptide are placed canyon between central C-terminal domains. adopts well-defined conformation establishes an extensive set interactions enzyme including invariant residues Glu64 Trp199, which together govern...