Develop more effective diet pills! Shanghai University of Science and Technology co-research results on the latest "Science"

▎ in the latest issue of science, a top academic journal edited by the content team of YaoMing Kant, Shanghai University of science and technology, together with researchers from the University of Michigan and the University of Southern California, published an important paper, bringing good news to obese patients.scientists have for the first time revealed the precise shape of a protein in the human brain.in view of the key role of this protein in the metabolic process, based on this achievement, future researchers will be able to develop more effective drugs to treat obesity and other metabolic diseases.the protagonist of this study is called melanocortin receptor 4 (MC4R).the melanocortin system has a far-reaching impact on the body weight regulation in the state of health and disease (including obesity and cancer).its receptor MC4R is mainly distributed in the hypothalamus, which plays a key role in the control of food intake, energy consumption and weight maintenance.previous studies have shown that mutations in the gene encoding MC4R are the most common genetic defects that cause obesity, especially in children, with about 1 in 1500 affected.abnormal MC4R pathway may also lead to overeating."many people think that obesity is caused by lifestyle, but it is not always the case.some people have mutations in this gene.people with this gene mutation often have no control over their food intake.it is this receptor that causes problems in the brain."Professor Raymond Stevens of the ihuman Institute, Shanghai University of science and technology, said.Image Source: pixabay although MC4R has long been regarded as an important drug target for obesity, drug design for this receptor protein is challenging.at present, there are only a few drugs designed to target MC4R. One of the drugs under study, setmelanotide, is only aimed at some relatively rare obesity types, and can not be applied to treat a wider range of obesity types, such as diet induced obesity.identifying the precise structure of MC4R, understanding how this receptor binds to other molecules and the characteristics of their interactions will help scientists develop and test new weight loss drugs.this is the significance of this study. the researchers analyzed the crystal structure of the complex of MC4R and shu9119, and found that calcium ion plays an unexpected role in the binding of MC4R to ligand. specifically, calcium ion binding in the MC4R positive binding pocket interacts with the receptor and the candidate drug, which helps to stabilize the receptor candidate drug complex and greatly improves the affinity and potency of endogenous agonists. } the structure of the complex of MC4R and shu9119 (photo source: reference [1]) indicates that this is the first time to observe the binding mode of functional calcium ion with G protein coupled receptor. Professor Stevens compared the relationship between receptor and ligand to lock and key, while calcium ion was like an extra small key. "Here, we found that opening the receptor requires a big key and a small key". "MC4R is a mysterious and interesting protein molecule, and there are many undiscovered stories. the composite structure of mc4r-shu9119 calcium ion has lifted the mystery of MC4R for the first time. "said Yu Jing, the first author of the study. according to the author, the structure of activated state, the interaction between MC4R and G protein, and other proteins will be further studied. } is expected to bring new weight loss drugs based on structural design (photo sources: reference [3]; Credit: yekaterina kadyshevskaya), which undoubtedly attracts the attention of many drug developers. Mr. Lex van der Ploeg was the chief scientific officer of rhythmpharmaceuticals, and the weight-loss drug, setmelanotide, mentioned earlier, is a candidate drug of this biomedical company. he said that the findings of this study open up a new way to design agonists and antagonists of melanocortin receptor family based on structure. we look forward to the follow-up research of researchers to bring new weight loss drugs as soon as possible, so that more people can avoid the problems and health threats caused by obesity. reference [1] Jing Yu et al. (2020) determination of the melanocortin-4 receptor structure identities Ca2 + as a cofactor for life binding. Science. Discovery of protein's configuration could lead to more effective anti-compliance treatments. Retrieved Apr. 24, 2020, From anobsity protein discovery may lead to better treatments. Retrieved Apr. 24, 2020, from! Retrieved Apr. 24, 2020, from