Structural Insights into the Substrate Binding of Farnesyl Diphosphate Synthase FPPS1 from Silkworm, Bombyx mori.

Abstract

Farnesyl diphosphate synthase (FPPS) is an important enzyme involved in the juvenile hormone (JH) biosynthesis pathway. Herein, we report the crystal structure of a type-I Lepidopteran FPPS from Bombyx mori (BmFPPS1) at 2.80 Å resolution. BmFPPS1 adopts an α-helix structure with a deep cavity at the center of the overall structure. Computational simulations combined with biochemical analysis allowed us to define the binding mode of BmFPPS1 to its substrates. Structural comparison revealed that BmFPPS1 adopts a structural pattern similar to that of type-II FPPS but exhibits a distinct substrate-binding site. These findings provide a structural basis for understanding substrate preferences and designing FPPS inhibitors. Furthermore, the expression profiles and RNA interference of BmFPPSs indicated that they play critical roles in the JH biosynthesis and larval-pupal metamorphosis. These findings enhance our understanding of the structural features of type-I Lepidopteran FPPS while providing direct evidence for the physiological role of BmFPPSs in silkworm development.