Structural highlights
Function
D3DUW7_HUMAN
Publication Abstract from PubMed
Mitochondrial dysfunction has been attributed to many disease indications, including metabolic, cardiovascular, neoplastic, and neurodegenerative diseases. Dynamin related protein 1 (DRP1) is crucial in regulating mitochondrial fission and maintaining mitochondrial homeostasis. MiD49 is a dynamic peripheral protein receptor on the surface of the mitochondrial membrane that recruits DRP1 protein to induce mitochondrial binary fission. By targeting the protein-protein interaction of DRP1/MiD49, we have discovered a novel and potent allosteric DRP1 inhibitor that inhibits mitochondria fragmentation in vitro. X-ray cocrystal structure revealed that it locked the closed DRP1 conformation by induced dimerization.
Discovery of Potent Allosteric DRP1 Inhibitors by Disrupting Protein-Protein Interaction with MiD49.,Furuya T, Lin J, Afanaseva A, Molz L, Lagu B, Ma B ACS Med Chem Lett. 2023 Jul 24;14(8):1095-1099. doi: , 10.1021/acsmedchemlett.3c00223. eCollection 2023 Aug 10. PMID:37583827[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Furuya T, Lin J, Afanaseva A, Molz L, Lagu B, Ma B. Discovery of Potent Allosteric DRP1 Inhibitors by Disrupting Protein-Protein Interaction with MiD49. ACS Med Chem Lett. 2023 Jul 24;14(8):1095-1099. PMID:37583827 doi:10.1021/acsmedchemlett.3c00223
