Structural characterization and functional analysis of juvenile hormone acid methyltransferase JHAMT3 from the silkworm, Bombyx mori.

Li Zhang, Haiyang Xu, Yunshi Zhang, Huan Zhang, Zhan Wang, Pengchao Guo, Ping Zhao

Insect biochemistry and molecular biology 2022 Dec

filter terms:

Juvenile hormone acid methyltransferase (JHAMT) is a rate-limiting enzyme of juvenile hormone (JH) biosynthesis in insects. It transfers the methyl group of S-adenosyl methionine to either the carboxyl group of JH acids or farnesoic acid to produce JH. Six JHAMT paralogues have been identified in the silkworm (Bombyx mori); among them, JHAMT1 and JHAMT2 display a methyltransferase activity. Here, the three-dimensional crystal structure of inactive JHAMT3 and the binary complex of JHAMT3 with its cofactor S-adenosyl-l-homocysteine were determined through X-ray crystallization. Comparative structural analysis revealed that JHAMT3 adopted a similar structural pattern to that of functional JHAMT2, which comprised one core Rossmann fold domain and one substrate-binding domain. Similar to JHAMT2, JHAMT3 underwent a conformational change at the Rossmann fold domain because of cofactor binding, which promoted ligand accommodation. However, it exhibited a relatively rigid substrate-binding pocket compared with that of JHAMT2. JHAMT3 was also highly expressed in the silk gland of fourth- and fifth-instar B. mori larvae. The results of expression profiling combined with activity analysis suggested that JHAMT3 might function as a binding protein of JH acids for the regulation of JH acid titers. These findings provide a structural basis for enhancing the understanding of the physiological function of JHAMT3 and a rational framework for the development of potent and specific inhibitors of JHAMT family members. Copyright © 2022 Elsevier Ltd. All rights reserved.

Citation

Li Zhang, Haiyang Xu, Yunshi Zhang, Huan Zhang, Zhan Wang, Pengchao Guo, Ping Zhao. Structural characterization and functional analysis of juvenile hormone acid methyltransferase JHAMT3 from the silkworm, Bombyx mori. Insect biochemistry and molecular biology. 2022 Dec;151:103863