Structural Insights into the Substrate Binding of Farnesyl Diphosphate Synthase FPPS1 from Silkworm, Bombyx mori.
Structural Insights into the Substrate Binding of Farnesyl Diphosphate Synthase FPPS1 from Silkworm, Bombyx mori.
复制标题
家蚕法尼基二磷酸合酶 FPPS1 底物结合的结构见解。
DOI：
10.1021/acs.jafc.3c06741
复制
发表时间：
2024
影响因子：
6.1
通讯作者：
P. Guo
中科院分区：
文献类型：
--
作者：
Huan Fang;Haogang Zheng;Yuanyuan Yang;Ying Hu;Zhan Wang;Qingyou Xia;P. Guo
法呢基二磷酸合酶（FPPS）是保幼激素（JH）生物合成途径中的重要酶。本文报道了一种鳞翅目昆虫家蚕FPPS（BmFPPS 1）的晶体结构，分辨率为2.80 nm。BmFPPS 1采用α-螺旋结构，在整体结构的中心有一个深腔。计算模拟结合生化分析，使我们能够定义BmFPPS 1的结合模式，其基板。结构比较显示，BmFPPS 1采用类似于II型FPPS的结构模式，但具有不同的底物结合位点。这些发现为理解底物偏好和设计FPPS抑制剂提供了结构基础。BmFPPSs的表达谱和RNA干扰结果表明，BmFPPSs在JH生物合成和幼虫-蛹变态过程中起重要作用。这些发现增强了我们对I型鳞翅目昆虫FPPS结构特征的理解，同时为BmFPPS在家蚕发育中的生理作用提供了直接证据。
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.
影响因子：
10.7
作者：
Kumar, Sudhir;Stecher, Glen;Tamura, Koichiro
通讯作者：
Tamura, Koichiro
DOI：
10.1073/pnas.91.8.3044
发表时间：
1994-04-12
影响因子：
11.1
作者：
SONG, LS;POULTER, CD
通讯作者：
POULTER, CD