September 21 2021
We would like to inform you that the 73rd IRCMS seminar has been scheduled as below. We would be pleased to see many of you participating in the seminar.
Date : September 29, 2021 (Wednesday)
Time : 16:00-17:00
* To prevent the spread of COVID-19, it will be a Zoom-based online seminar.
Speaker : Makoto Suematsu, MD, PhD
Professor and Chair
Department of Biochemistry,
Keio University School of Medicine
Tilte : Metabolites as molecular glues to trigger protein-protein interactions that regulate diseases
Small molecular metabolites are utilized for energy sources, substrates and allosteric regulators for enzyme reactions. However, discovery of cerebron, ubiquitin E3 ligase, as a thalidomide-binding protein and development of medicines to cure leukemic diseases has changed the paradigm. Thalidomide contains a characteristic hetero-bifunctional structure including uridine for allowing cerebron to bind, and the opposite moiety for binding of target molecules of hematopoietic malignancy. Such hetero-bifunctional actions of thalidomide to make two different proteins close to each other result in degradation of the target proteins by cerebron to cure diseases. We attempted to reversely translate these findings into roles of hetero-bifunctional metabolites in forming or degrading protein complexes as a novel role of small molecular metabolites. Imaging metabolomics enables to reveal candidates of hetero-bifunctional metabolites which are present at extremely high concentrations. Among candidates, chemical biology using affinity nanobeads enables to identify list of proteins that can bind to the candidate metabolites. Such approaches for discovering metabolite-protein interactions allowed us to identify that heme is such a hetero-bifunctional metabolites that regulate monomer/dimer transition of PGRMC families to control diseases. Imaging metabolomics combined with chemical biology serves as a powerful approach to mine unidentified interactions between metabolites and proteins to further understand mechanisms of diseases.
Kabe Y, Suematsu M, et al. Nature Communications 2016.
Shiota M, Suematsu M, et al. Nature Communications 2018.
Furuhata R, Suematsu M, et al. Communications Biology 2020.
Kabe Y, Suematsu M, et al. Cancers 2021.
Anyone in Kumamoto University who wants to join is welcome; however, please pre-register by the following URL to secure your seat or receive the Zoom meeting information.
Flyer (Click for a larger image):