Author: Wu Changfeng Date: 2019-02-20 The reporter learned from the University of Science and Technology of China that the research group of the school, Long Dong, used liquid NMR spectroscopy to make important new progress in the field of allosteric dynamics of oncoprotein Ras. The relevant results were published in the academic journal "German application". Chemistry". As a key signal transduction molecule in the cell, the change of Ras protein activity is closely related to the occurrence of human malignant tumor, and it has become an important target for the development of anticancer drugs. The Ras site-specific kinetics information in the binding state of natural GTP molecules is crucial for the deep understanding of its signal transduction mechanism and related inhibitor research, but its activity status is extremely unstable due to the GTP activity of Ras itself. It is not easy to study. Longdong's group obtained the direct kinetic evidence of Ras asymmetric nucleoside exchange reaction mediated by Sos through real-time nuclear magnetic resonance experiments, and used this reaction direction to selectively develop an activity state that can prolong the oncogene protein Ras. An effective experimental method makes it possible to measure multidimensional nuclear magnetic spectroscopy for the natural active state of Ras. On this basis, the team achieved the main chain signal assignment of the near-full site (97%) of the natural Ras-GTP complex; and applied a spin-relaxed NMR method and a newly developed digital signal. The processing technique obtains the conformational dynamics of the Ras natural active state on a millisecond time scale. The dynamic network of Ras co-conformation revealed in this work covers important allosteric inhibitor binding sites discovered in recent years, supporting the conformational selection theory of intermolecular recognition. This study further elucidated the conformational dynamic properties of Ras naturally active state, which laid an important foundation for the complete understanding and regulation of Ras signal transduction activity. The project was funded by the Ministry of Science and Technology, the Fund Committee and the central university's basic research business fees. (Reporter Wu Changfeng) Source: Technology Daily
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Revealing kinetic mechanism of oncogene protein Ras