著者
Kotaro Koiwai Kana Morohashi Kazue Inaba Kana Ebihara Hirotatsu Kojima Takayoshi Okabe Ryunosuke Yoshino Takatsugu Hirokawa Taiki Nampo Yuuta Fujikawa Hideshi Inoue Fumiaki Yumoto Toshiya Senda Ryusuke Niwa
出版者
Pesticide Science Society of Japan
雑誌
Journal of Pesticide Science (ISSN:1348589X)
巻号頁・発行日
vol.46, no.1, pp.75-87, 2021-02-20 (Released:2021-02-26)
参考文献数
40
被引用文献数
6

Insect growth regulators (IGRs) can be developed by elucidating the molecular mechanisms of insect-specific biological events. Because insect molting, and metamorphosis are controlled by ecdysteroids, their biosynthetic pathways can serve as targets for IGR development. The glutathione S-transferase Noppera-bo (Nobo), which is conserved in dipteran and lepidopteran species, plays an essential role in ecdysteroid biosynthesis. Our previous study using 17β-estradiol as a molecular probe revealed that Asp113 of Drosophila melanogaster Nobo (DmNobo) is essential for its biological function. However, to develop IGRs with a greater Nobo inhibitory activity than 17β-estradiol, further structural information is warranted. Here, we report five novel non-steroidal DmNobo inhibitors. Analysis of crystal structures of complexes revealed that DmNobo binds these inhibitors in an Asp113-independent manner. Among amino acid residues at the substrate-recognition site, conformation of conserved Phe39 was dynamically altered upon inhibitor binding. Therefore, these inhibitors can serve as seed compounds for IGR development.
著者
Kotaro Koiwai Kana Morohashi Kazue Inaba Kana Ebihara Hirotatsu Kojima Takayoshi Okabe Ryunosuke Yoshino Takatsugu Hirokawa Taiki Nampo Yuuta Fujikawa Hideshi Inoue Fumiaki Yumoto Toshiya Senda Ryusuke Niwa
出版者
Pesticide Science Society of Japan
雑誌
Journal of Pesticide Science (ISSN:1348589X)
巻号頁・発行日
pp.D20-072, (Released:2021-02-04)
参考文献数
40
被引用文献数
6

Insect growth regulators (IGRs) can be developed by elucidating the molecular mechanisms of insect-specific biological events. Because insect molting, and metamorphosis are controlled by ecdysteroids, their biosynthetic pathways can serve as targets for IGR development. The glutathione S-transferase Noppera-bo (Nobo), which is conserved in dipteran and lepidopteran species, plays an essential role in ecdysteroid biosynthesis. Our previous study using 17β-estradiol as a molecular probe revealed that Asp113 of Drosophila melanogaster Nobo (DmNobo) is essential for its biological function. However, to develop IGRs with a greater Nobo inhibitory activity than 17β-estradiol, further structural information is warranted. Here, we report five novel non-steroidal DmNobo inhibitors. Analysis of crystal structures of complexes revealed that DmNobo binds these inhibitors in an Asp113-independent manner. Among amino acid residues at the substrate-recognition site, conformation of conserved Phe39 was dynamically altered upon inhibitor binding. Therefore, these inhibitors can serve as seed compounds for IGR development.