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Étude structurale de l’histoneméthyltransférase « CARM1 » et de ses complexes biologiquement significatifs : des structures 3D vers la conception rationnelle de composés à action pharmacologique

Abstract : Protein arginine methyltransferases (PRMTs) are involved in several cellular mechanisms: transcription, RNA maturation and transport, translation, signal transduction, DNA replication and repair, and apoptosis. Different studies showed that deregulation of those mechanisms involving PRMTs can induce some cancers, making these enzymes new potential targets for chemotherapy. It is therefore crucial to understand the mode of action of PRMTs at the atomic scale, both at the fundamental level and for the development of new drugs. The studies described here focus on PRMT4/CARM1 and rely on structural studies by bio-crystallography, in order to understand the methylation mechanisms catalyzed by CARM1 and to discover specific inhibitors, but also on in vitro studies, to characterize the interaction between CARM1 and its substrates.
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Justine Mailliot. Étude structurale de l’histoneméthyltransférase « CARM1 » et de ses complexes biologiquement significatifs : des structures 3D vers la conception rationnelle de composés à action pharmacologique. Sciences agricoles. Université de Strasbourg, 2013. Français. ⟨NNT : 2013STRAJ015⟩. ⟨tel-00986266⟩

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