期刊
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
卷 151, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.ibmb.2022.103863
关键词
Juvenile hormone biosynthesis; Crystal structure; Conformational change; Expression profile; Binding affinity
资金
- National Natural Science Foundation of China [31970468, 32030103]
- Natural Science Foundation of Chongqing, China [cstc2020jcyj-cxttX0001]
- Venture and Innovation Support Program for Chongqing Overseas Returnees [cx2020100]
This study determined the three-dimensional crystal structure of JHAMT3 and its binding properties. The results revealed that JHAMT3 shares a similar structural pattern with functional JHAMT2 and is highly expressed in the silk gland of Bombyx mori larvae. It is suggested that JHAMT3 may function as a binding protein for the regulation of juvenile hormone acid levels.
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-homo-cysteine 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.
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