Crystal Structure and Potential Head-to-Middle Condensation Function of a Z,Z-Farnesyl Diphosphate Synthase.

Crystal Structure and Potential Head-to-Middle Condensation Function of a Z,Z-Farnesyl Diphosphate Synthase.
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DOI:
10.1021/acsomega.6b00562
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发表时间:
2017-03-31
期刊:
影响因子:
4.1
通讯作者:
Wang AH
Wang AH
中科院分区:
化学3区
文献类型:
--
作者:
Chan YT;Ko TP;Yao SH;Chen YW;Lee CC;Wang AH

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植物产生各种各样的次生代谢产物以响应不利的环境因素。由Z,Z-法呢基二磷酸合成酶(zFPS)合成的Z,Z-法呢基二磷酸(Z,Z-FPP)支持野生番茄中植物化学物质的形成。在此,确定了N-末端截短的zFPS(ΔzFPS)的晶体结构。除了N端截短的结构外,基于结构分析和突变分析还发现ΔzFPS中的H103残基是这种不规则功能的关键元件之一。通过与异戊烯基二磷酸、二甲基烯丙基硫代二磷酸或两者共结晶,从Δ zFPS-H103 Y获得一系列底物-酶复合物结构。不同的底物结合模式被揭示。提出了ΔzFPS中头-尾反应和头-中反应的催化机理。阐明了该酶中两种机制之间的功能转换以及柔性C端所起的重要作用。
Plants produce a wide variety of secondary metabolites in response to adverse environmental factors. Z,Z-Farnesyl diphosphate (Z,Z-FPP), synthesized by Z,Z-farnesyl diphosphate synthase (zFPS), supports the formation of phytochemicals in wild tomatoes. Here, the crystal structure of N-terminal truncated zFPS (ΔzFPS) was determined. Irregular products including lavandulyl diphosphate and an unknown compound were surprisingly found. Apart from the truncated N-terminus as a functional regulator, structure-based analysis and mutagenesis assays revealed a residue H103 in ΔzFPS as one of the key elements to this irregular function. A series of substrate–enzyme complex structures were obtained from ΔzFPS-H103Y by co-crystallizing with isopentenyl diphosphate, dimethylallyl thiolodiphosphate, or both. Various substrate-binding modes were revealed. The catalytic mechanisms of both the head-to-tail and head-to-middle reactions in ΔzFPS were proposed. Functional switch between the two mechanisms in this enzyme and the essential role played by the flexible C-terminus were elucidated as well.
结核菌合酶的结构和抑制作用和二磷酸二磷酸合酶从结核分枝杆菌。
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