7EBX

Crystal structure of juvenile hormone acid methyltransferase JHAMT in complex with S-adenosyl-L-homocysteine.

7EBX の概要

• エントリーDOI: 10.2210/pdb7ebx/pdb
• 分子名称: juvenile hormone acid methyltransferase, S-ADENOSYL-L-HOMOCYSTEINE (3 entities in total)
• 機能のキーワード: juvenile hormone, methyltransferase, comolex, insects, hormone
• 由来する生物種: Bombyx mori
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 31967.58

構造登録者

Guo, P.C.,Zhang, Y.S.,Zhang, L.,Xu, H.Y.,Xia, Q.Y. (登録日: 2021-03-11, 公開日: 2021-09-29, 最終更新日: 2024-11-13)

主引用文献

Guo, P.,Zhang, Y.,Zhang, L.,Xu, H.,Zhang, H.,Wang, Z.,Jiang, Y.,Molloy, D.,Zhao, P.,Xia, Q.
Structural basis for juvenile hormone biosynthesis by the juvenile hormone acid methyltransferase.
J.Biol.Chem., 297:101234-101234, 2021

PubMed Abstract: Juvenile hormone (JH) acid methyltransferase (JHAMT) is a rate-limiting enzyme that converts JH acids or inactive precursors of JHs to active JHs at the final step of JH biosynthesis in insects and thus presents an excellent target for the development of insect growth regulators or insecticides. However, the three-dimensional properties and catalytic mechanism of this enzyme are not known. Herein, we report the crystal structure of the JHAMT apoenzyme, the three-dimensional holoprotein in binary complex with its cofactor S-adenosyl-l-homocysteine, and the ternary complex with S-adenosyl-l-homocysteine and its substrate methyl farnesoate. These structures reveal the ultrafine definition of the binding patterns for JHAMT with its substrate/cofactor. Comparative structural analyses led to novel findings concerning the structural specificity of the progressive conformational changes required for binding interactions that are induced in the presence of cofactor and substrate. Importantly, structural and biochemical analyses enabled identification of one strictly conserved catalytic Gln/His pair within JHAMTs required for catalysis and further provide a molecular basis for substrate recognition and the catalytic mechanism of JHAMTs. These findings lay the foundation for the mechanistic understanding of JH biosynthesis by JHAMTs and provide a rational framework for the discovery and development of specific JHAMT inhibitors as insect growth regulators or insecticides.

PubMed: 34562453
DOI: 10.1016/j.jbc.2021.101234

実験手法

X-RAY DIFFRACTION (2.89 Å)