8SKN

Crystal structure of compound 3-bound human Dynamin-1-like protein GTPase-BSE fusion

Summary for 8SKN

• Entry DOI: 10.2210/pdb8skn/pdb
• Descriptor: Dynamin-1-like protein GTPase-BSE fusion, N-[4-(azetidin-1-yl)-2-(4-methylphenyl)quinolin-6-yl]-2-methylpropanamide, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: inhibitor, hydrolase-inhibitor complex, hydrolase/inhibitor
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 86161.53

Authors

Ma, B. (deposition date: 2023-04-20, release date: 2023-08-30)

Primary citation

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., 14:1095-1099, 2023

PubMed Abstract: 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 . X-ray cocrystal structure revealed that it locked the closed DRP1 conformation by induced dimerization.

PubMed: 37583827
DOI: 10.1021/acsmedchemlett.3c00223

Experimental method

X-RAY DIFFRACTION (2.41 Å)