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Mechanism of action of mitofusin activators. A. Computational model of PPI-regulated conformational changes in human MFN2. (inset) Published pharmacophore model described by E. Gavathiotis17, 18 positing specific amino acid interactions of the green MFN2-derived activator minipeptide. B. A prototype small molecule mitofusin activator, 1, was developed that mimics characteristics of critical amino acid side chains of the mitofusin activating minipeptide.18
