Department of Bioscience and Biotechnology, Kyushu University Graduate School, 744 Motooka, Nishi-ku, Fukuoka, 819- 0395, Fukuoka, Japan.
Protein J. 2021 Feb;40(1):63-67. doi: 10.1007/s10930-020-09956-3. Epub 2021 Jan 5.
Prostaglandin E synthase (PGES) catalyzes the conversion of prostaglandin H to prostaglandin E in the presence of glutathione (GSH) in mammals. Amid the limited knowledge on prostaglandin and its related enzymes in insects, we recently identified PGES from the silkworm Bombyx mori (bmPGES) and determined its crystal structure complexed with GSH. In the current study, we investigated the substrate-binding site of bmPGES by site-directed mutagenesis and X-ray crystallography. We found that the residues Tyr107, Val155, Met159, and Glu203 are located in the catalytic pockets of bmPGES, and mutagenesis of each residue reduced the bmPGES activity. Our results suggest that these four residues contribute to the catalytic activity of bmPGES. Overall, this structure-function study holds implications in controlling pests by designing rational and efficient pesticides.
前列腺素 E 合酶（PGES）在哺乳动物中，在谷胱甘肽（GSH）的存在下催化前列腺素 H 转化为前列腺素 E。在对昆虫中前列腺素及其相关酶的有限了解的情况下，我们最近从家蚕（Bombyx mori）中鉴定出前列腺素 E 合酶（bmPGES），并确定了其与 GSH 结合的晶体结构。在本研究中，我们通过定点突变和 X 射线晶体学研究了 bmPGES 的底物结合位点。我们发现残基 Tyr107、Val155、Met159 和 Glu203 位于 bmPGES 的催化口袋中，每个残基的突变都会降低 bmPGES 的活性。我们的结果表明，这四个残基对 bmPGES 的催化活性有贡献。总的来说，这项结构-功能研究对通过设计合理有效的杀虫剂来控制害虫具有重要意义。
