A5016702037- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Cell Image Analysis Techniques
- Computational Drug Discovery Methods
- Innovative Microfluidic and Catalytic Techniques Innovation
- Sexuality, Behavior, and Technology
- Evolutionary Psychology and Human Behavior
- Sexual function and dysfunction studies
- Pancreatic function and diabetes
- Calcium signaling and nucleotide metabolism
- Advanced Biosensing Techniques and Applications
- Adenosine and Purinergic Signaling
Novartis (United States)
2024
University of California, Los Angeles
2014-2023
Novartis (Switzerland)
2023
Novartis Institutes for BioMedical Research
2023
University of Nicosia
2023
The human genome encodes a family of nine protein arginine methyltransferases (PRMT1–9), whose members can catalyse three distinct types methylation on residues. Here we identify two spliceosome-associated proteins—SAP145 and SAP49—as PRMT9-binding partners, linking PRMT9 to U2 snRNP maturation. We show that SAP145 is methylated by at 508, which takes the form monomethylated (MMA) symmetrically dimethylated (SDMA). thus joins PRMT5 as only mammalian enzymes capable depositing SDMA mark....
The mammalian protein arginine methyltransferase 7 (PRMT7) has been implicated in roles of transcriptional regulation, DNA damage repair, RNA splicing, cell differentiation, and metastasis. However, the type reaction that it catalyzes its substrate specificity remain controversial. In this study, we purified a recombinant mouse PRMT7 expressed insect cells demonstrates robust activity. Using variety substrates, demonstrate enzyme only formation ω-monomethylarginine residues, confirm activity...
Protein arginine methyltransferase 7 (PRMT7) methylates residues on various protein substrates and is involved in DNA transcription, RNA splicing, repair, cell differentiation, metastasis. The substrate sequences it recognizes vivo the enzymatic mechanism behind it, however, remain to be explored. Here we characterize methylation catalyzed by a bacterially expressed GST-tagged human PRMT7 fusion with broad range of peptide substrates. After confirming its type III activity generating only...
Less studied than the other protein arginine methyltransferase isoforms, PRMT7 and PRMT9 have recently been identified as important therapeutic targets. Yet, most of their biological roles functions are still to be defined, well structural requirements that could drive identification selective modulators activity. We described led potent PRMT4 inhibitors spanning both substrate cosubstrate pockets. The reanalysis data suggested a preferential binding for shorter derivatives prompted us...
Phenotypic assays have become an established approach to drug discovery. Greater disease relevance is often achieved through cellular models with increased complexity and more detailed readouts, such as gene expression or advanced imaging. However, the intricate nature cost of these impose limitations on their screening capacity, restricting screens well-characterized small compound sets chemogenomics libraries. Here, we outline a cheminformatics identify set compounds likely novel...
Caenorhabditis elegans protein arginine methyltransferases PRMT-7 and PRMT-9 are two evolutionarily conserved enzymes, with distinct orthologs in plants, invertebrates, vertebrates. Biochemical characterization of these enzymes reveals that they share much common their mammalian orthologs. C. produces only monomethylarginine (MMA) preferentially methylates R-X-R motifs a broad collection substrates, including human histone peptides RG-rich peptides. In addition, the activity enzyme is...
Protein arginine methyltransferases (PRMTs) make up a family of enzymes that transfer methyl groups onto residues and play important roles in DNA repair, splicing, transcriptional control signaling. In mammals, nine PRMTs are known. PRMT1,2,3,4,6, 8 catalyze the formation asymmetric dimethylarginine (ADMA) w‐monomethylarginine (MMA), PRMT5 catalyzes symmetric (SDMA) MMA formation, PRMT7 only formation. The last member this family, PRMT9 (also designated PRMT10), has not previously been...
Identifying high quality chemical starting points is a critical and challenging step in drug discovery, which typically involves screening large compound libraries or repurposing of compounds with known mechanisms actions (MoAs). Here we introduce novel cheminformatics approach that mines existing large-scale, phenotypic throughput (HTS) data. Our method aims to identify bioactive distinct specific MoAs, serving as valuable complement focused library collections. This identifies chemotypes...
Identifying high quality chemical starting points is a critical and challenging step in drug discovery, which typically involves screening large compound libraries or repurposing of compounds with known mechanisms actions (MoAs). Here we introduce novel cheminformatics approach that mines existing large-scale, phenotypic throughput (HTS) data. Our method aims to identify bioactive distinct specific MoAs, serving as valuable complement focused library collections. This identifies chemotypes...
Protein arginine methyltransferases (PRMTs) make up a family of enzymes that transfer methyl groups onto residues and play important roles in DNA repair, splicing, transcriptional control signaling. In mammals, nine PRMTs are known. PRMT1,2,3,4,6, 8 catalyze the formation asymmetric dimethylarginine (ADMA) ω‐monomethylarginine (MMA), PRMT5 catalyzes symmetric (SDMA) MMA formation, PRMT7 only formation. The last member this family, PRMT9 (also designated PRMT10), has not previously been...
Protein arginine methylation is a widespread and important posttranslational modification in eukaryotic cells, shown to be involved the activation or repression of transcription, splicing machinery, signaling, DNA repair. Mammalian protein methyltransferases include family nine sequence‐related enzymes that transfer one two methyl groups onto terminal guanidino on residues, producing monomethylarginine only (MMA, type III), symmetric dimethylarginine (SDMA) MMA (Type II), asymmetric (ADMA)...
Abstract Invertebrate model organisms (the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster ) are valuable tools to bridge gap between traditional in vitro discovery preclinical animal models. poised serve as better disease models than 2D cellular monocultures for drug discovery, well easier more cost-effective scale up 3D organoids/assembloids or co-cultures. A strength of is opportunity probe conserved biology such lysosomal function autophagy a physiological...