Russian scientists in conjunction with colleagues from the United States have identified the structure of the BLT1 leukotriene receptor, which participates in inflammatory processes and plays a role in the development of infectious, allergic and tumor diseases. The results of a study published in the Nature Communications journal open a new way to developing methods for the treatment of 2-type diabetes.
Experts found that BLT1 is associated with a number of diseases, including asthma, influenza, arthritis, atherosclerosis, diabetes and cancer. Although attempts were repeatedly made to use the receptor as a target for medicines, potential drugs have a number of undesirable side effects, low efficiency and long-elimination of the body.
researchers presented the crystal structure of the human BLT1 (HBLT1) in a complex with a selective antagonist MK-D-046, developed for the treatment of diabetes of the 2nd type and other inflammatory states. They analyzed the relationship between the structure and the activity of the receptor with the help of intentional mutations in key areas of molecules, and determined the mechanism for binding to various subtypes of the receptor with ligands – small molecules that form complex complexes together with BLT1.
How do the authors of the work, knowledge of the structure helps to identify the ligand access channel hidden in the furnace cell to the receptor, as well as determine the possible ways of binding to the receptor. This gives an understanding of how Ligands recognize BLT1, and opens up new opportunities for drug development.