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Publication Abstract from PubMed

Autophagy-associated protein 8 (ATG8) is essential for autophagy and organismal growth and development. In this study, we successfully resolved the crystal structure of Drosophila melanogaster (D. melanogaster) ATG8a (DmATG8a) at 1.36 A resolution. Being distinct from previously characterized ATG8 homologues, DmATG8a (121 residues) adopts a unique fold comprising five alpha-helices and four beta-folding strands, in contrast to the canonical four alpha-helices and four beta-folding strands observed in other ATG8 proteins. DmATG8a features two active cavities: hydrophobic pocket 1 (HP1) and hydrophobic pocket 2 (HP2), which are essential for the normal physiological function of ATG8. Indole and its analogs can bind specifically with HP1. Microscale thermophoresis results demonstrated a strong affinity of 6-fluoroindole with DmATG8a (3.54 mumol/L), but no affinity with the DmATG8a(K48A) mutant, suggesting that Lys48 is critical in binding 6-fluoroindole probably via a hydrogen bond interaction. The half-maximum lethal concentration (LC(50)) of 6-fluoroindole against D. melanogaster adult flies was 169 mug/mL. Our findings establish DmATG8a as a promising target for developing indole-based insecticides.

Crystal Structure of Autophagy-Associated Protein 8 at 1.36 A Resolution and Its Inhibitory Interactions with Indole Analogs.,Zhang S, Luo X, Yuan X, Wu D, Liu J, Zhao K, Xu Y, Zhou J, Li X, Li QX J Agric Food Chem. 2025 Mar 26;73(12):7111-7120. doi: 10.1021/acs.jafc.4c11205. , Epub 2025 Mar 11. PMID:40066832^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.