莎梵婷
热休克蛋白90
热休克蛋白
生物化学
酵母
化学
大肠杆菌
脂肽
细胞生物学
ATP水解
环肽
细菌
生物
生物物理学
肽
酶
枯草芽孢杆菌
ATP酶
基因
遗传学
作者
Hitoshi Nakamoto,Yuhei Yokoyama,Takahiro Suzuki,Yuri Miyamoto,Takashi Fujishiro,Masaaki Morikawa,Yoshihiko Miyata
摘要
Abstract Heat shock protein 90 (Hsp90) is essential for eukaryotic cells, whereas bacterial homologs play a role under stresses and in pathogenesis. Identifying species-specific Hsp90 inhibitors is challenging because Hsp90 is evolutionarily conserved. We found that a cyclic lipopeptide surfactin inhibits the ATPase activity of Hsp90 from the cyanobacterium Synechococcus elongatus (S.elongatus) PCC 7942 but does not inhibit Escherichia coli (E.coli), yeast and human Hsp90s. Molecular docking simulations indicated that surfactin could bind to the N-terminal dimerization interface of the cyanobacterial Hsp90 in the ATP- and ADP-bound states, which provided molecular insights into the species-selective inhibition. The data suggest that surfactin inhibits a rate-limiting conformational change of S.elongatus Hsp90 in the ATP hydrolysis. Surfactin also inhibited the interaction of the cyanobacterial Hsp90 with a model substrate, and suppressed S.elongatus growth under heat stress, but not that of E.coli. Surfactin did not show significant cellular toxicity towards mammalian cells. These results indicate that surfactin inhibits the cellular function of Hsp90 specifically in the cyanobacterium. The present study shows that a cyclic peptide has a great specificity to interact with a specific homolog of a highly conserved protein family.
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