Hokkaido University Monitoring changes in protein conformation-University Journal Online

New drug development

Kumamoto University Ishikawa Prefectural University Hokkaido University Waseda University Osaka University

A research group consisting of Hokkaido University, Ishikawa Prefectural University, Kumamoto University, Waseda University, Osaka University, and Shionogi Pharmaceutical has succeeded in observing how proteins change their three-dimensional structure during enzymatic reactions.Since the protein used in this study plays an important role in the growth of bacteria, it is expected to lead to the development of new antibacterial agents.

　Antibiotics inhibit the synthesis of the cell wall required for bacterial growth.Since there is no cell wall in animals such as humans, it has the characteristic of acting only on bacteria and is widely used for the treatment of bacterial infections.However, in rare cases, bacteria with resistance to antibiotics may be born, and bacteria that have acquired resistance to many drugs have also appeared.These resistant strains pose a major threat to the weak and inpatients.In order to deal with these infectious diseases, it is necessary to develop compounds with new antibacterial activity.

　The group focused on MurD, a protein involved in bacterial cell wall synthesis. If we can clarify how MurD changes its shape when synthesizing the cell wall, we can develop new antibiotics by designing substances that inhibit it.However, it was difficult to investigate structural changes in proteins with previous techniques.The group decided to investigate how MurD changes the three-dimensional structure by examining in detail the effect of the signal emitted by a metal called lanthanide on the measurement results by the conventional nuclear magnetic resonance (NMR) method. It was successful.

　The knowledge obtained this time is expected to be applied to the development of new drugs, and the measurement method using lanthanide can also be applied to elucidate various biological phenomena.It may be a breakthrough to create many new drugs beyond antibiotics.

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