New results promote the development of new drugs for diabetes

The Wu Yuli And Zhao Qiang research groups of the Shanghai Institute of Pharmaceutical Research of the Chinese Academy of Sciences have made important breakthroughs in the field of structure and function of type B G protein coupled mediators (GPCR), and for the first time measured the three-dimensional structure of the whole-length protein and polypeptide ligand complex of glucavin (GCGR), revealing the specific identification and active regulation mechanism of the subject to cell signal molecules. The results were published in the journal
4 January.
GPCR is the largest family of membrane-like proteins in the human body and play an important role in cell signal transducing. GPCR is closely related to human diseases, and more than 40% of drugs currently target GPCR. According to its similarity, GPCR can be divided into A, B, C and F and other four types. Type B GPCR includes a variety of important subject proteins such as GCGR, which identify and bind peptide hormones and is essential to maintain hormone balance in the body.
GCGR is an important target for the treatment of type 2 diabetes drugs, and its lack of structural information not only seriously restricts the understanding of the sensor signal recognition and transduction mechanism, but also greatly affects the drug research and development targeting GCGR. The researchers successfully analyzed the crystal structure of the complex combined with the full-length GCGR and the glutatroemia similarity NNC1702, revealing the fine pattern of the binding of type B GPCR with the polypeptide complex.
"The clarification of the interaction pattern between GCGR and peptide ligation will not only help to understand the mechanism of identification of cell signal molecules by type B GCR, but also provide the most accurate structural template to date for drug design targeting GCGR, which will greatly facilitate the development of new drugs for the treatment of type II diabetes," wu said.
The team also carried out a series of functional studies using a variety of technical means, such as the combination of subject, ligation competition, computer simulation and dual electron resonance, to clarify the dynamic changes of GCGR in different functional states, and to explore the regulatory mechanism of the reactiveization of the subject. Experts say the results will help to better understand the structural biological basis for the physiological effects of type B GPCR and accelerate the development of new drugs for type II diabetes. (Source: Science Network Huang Xin)