Application of new crystallization approaches and serial crystallography to the structural study of enzyme/tRNA complexes

Abstract : This thesis focuses on two complementary aspects, the development and implementation of new approaches of crystallization and of serial crystallography as well as their use in the structural study of enzymes/tRNA complexes. Crystallography is the most used method in structural biology, but it presents delicate points. Different methods were implemented in this work to overcome these points, which led to the resolution of the structure of the CCA-adding enzyme of the psychrophilic organism Planococcus halocryophilus and to the study of its structural adaptation to the cold; novel microfluidic crystallization chips that have been used for the resolution of several structures by serial crystallography at room-temperature; finally the Xtal Controller used for the study of nucleation and crystal growth events with the purpose of preparing samples for analysis under XFEL radiation. Among other biological systems, this thesis presents the study and characterization of two families of inhibitors targeting aspartyl-tRNA synthetases, including the one of the pathogenic organism Pseudomonas aeruginosa.
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Raphaël de Wijn. Application of new crystallization approaches and serial crystallography to the structural study of enzyme/tRNA complexes. Biophysics. Université de Strasbourg, 2018. English. ⟨NNT : 2018STRAJ095⟩. ⟨tel-02301381⟩

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