7XND

Crystal structure of Phosphomevalonate kinase from Silkworm

Summary for 7XND

• Entry DOI: 10.2210/pdb7xnd/pdb
• Descriptor: Phosphomevalonate kinase, GLYCEROL (3 entities in total)
• Functional Keywords: kinase, hormone synthesis, biosynthetic protein
• Biological source: Bombyx mori (domestic silkworm)
• Total number of polymer chains: 1
• Total formula weight: 24362.58

Authors

Guo, P.C.,Zhang, H. (deposition date: 2022-04-28, release date: 2023-05-03, Last modification date: 2023-11-29)

Primary citation

Zhang, H.,Liu, J.,Wang, H.,Fang, H.,Zhao, P.,Xia, Q.,Guo, P.
Structural insights into the substrate binding of phosphomevalonate kinase from the silkworm, Bombyx mori.
Insect Biochem.Mol.Biol., 150:103849-103849, 2022

PubMed Abstract: Phosphomevalonate kinase (PMK) is an important enzyme involved in the juvenile hormone (JH) biosynthesis pathway that catalyzes the phosphorylation of mevalonate 5-phosphate into mevalonate 5-diphosphate in the mevalonate pathway. Herein, we report the crystal structure of insect PMK from Bombyx mori (BmPMK) at a resolution of 1.60 Å. The overall structure of BmPMK adopts a compact α/β conformation with two parts: the core and lid regions. The interface between the core and lid regions forms a continuous and negatively charged groove to accommodate the substrates. Using computational simulation combined with site-directed mutagenesis and biochemical analysis, we define the binding mode of BmPMK with the cofactor and the substrate, which provides a structural basis for understanding the catalytic mechanism and the design of inhibitors of PMK. Moreover, BmPMK showed the optimal enzyme activity at pH 8.0, and the optimal temperature was 30 °C, using mevalonate 5-phosphate as the substrate. The expression profiles and kinetic analyses of BmPMK indicated that it plays critical role in the control of JH biosynthesis in silkworms. Collectively, these findings provide a better understanding of the structural and biochemical features of insect PMK.

PubMed: 36209956
DOI: 10.1016/j.ibmb.2022.103849

Experimental method

X-RAY DIFFRACTION (1.6 Å)