两种 I 型萜烯合成酶活性位点入口处的疏水隧道和守门员

IF 11.3 1区化学 Q1 CHEMISTRY, PHYSICAL

ACS Catalysis Pub Date : 2025-04-02 DOI:10.1021/acscatal.5c01540

Heng Li, Zhaoye Bai, Georges B. Tabekoueng, Baiying Xing, Bernd Goldfuss, Ming Ma, Donghui Yang, Jeroen S. Dickschat

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引用次数: 0

摘要

众所周知，二萜合成酶 SxSpS 能从香叶基二磷酸法呢基酯（GGPP）生成 spata-13,17-二烯，但也能将二磷酸法呢基酯（FPP）和 GFPP 转化为结构相似的萜烯。在这里，我们证明了 SxSpS 甚至能够从 FFPP 生成三萜。正如大量的对接研究所证明的那样，这种行为可以用晶体学上观察到的疏水隧道来解释，该隧道与活性位点相连，可以容纳非反应的旁观异戊二烯单元。该隧道的轮廓由三个小的氨基酸残基构成，它们与较大残基的系统交换破坏了对较高的低聚异戊烯二磷酸盐的接受。硒化-4(15),7(11)-二烯合成酶（SdS）中的一个类似隧道被一个守门员阻断，但通过定点突变打开该隧道可形成二萜。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

A Hydrophobic Tunnel and a Gatekeeper at the Active Site Entrance in Two Type I Terpene Synthases

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A Hydrophobic Tunnel and a Gatekeeper at the Active Site Entrance in Two Type I Terpene Synthases

The diterpene synthase SxSpS is known to produce spata-13,17-diene from geranylfarnesyl diphosphate (GGPP), but can also convert farnesyl diphosphate (FPP) and GFPP into structurally similar terpenes. Here we demonstrate that SxSpS is even able to produce a triterpene from FFPP. This behavior is explained by a hydrophobic tunnel observed crystallograpghically that is connected to the active site and can accommodate nonreacting spectator isoprenoid units, as demonstrated by extensive docking studies. The tunnel is contoured by three small amino acid residues, and their systematic exchange against larger residues disrupts the acceptance of higher oligoprenyl diphosphates. A similar tunnel in selina-4(15),7(11)-diene synthase (SdS) is blocked by a gatekeeper, but its opening through site-directed mutagenesis leads to formation of a diterpene.

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来源期刊

ACS Catalysis CHEMISTRY, PHYSICAL-

CiteScore

20.80

自引率

6.20%

发文量

1253

审稿时长

1.5 months

期刊介绍： ACS Catalysis is an esteemed journal that publishes original research in the fields of heterogeneous catalysis, molecular catalysis, and biocatalysis. It offers broad coverage across diverse areas such as life sciences, organometallics and synthesis, photochemistry and electrochemistry, drug discovery and synthesis, materials science, environmental protection, polymer discovery and synthesis, and energy and fuels. The scope of the journal is to showcase innovative work in various aspects of catalysis. This includes new reactions and novel synthetic approaches utilizing known catalysts, the discovery or modification of new catalysts, elucidation of catalytic mechanisms through cutting-edge investigations, practical enhancements of existing processes, as well as conceptual advances in the field. Contributions to ACS Catalysis can encompass both experimental and theoretical research focused on catalytic molecules, macromolecules, and materials that exhibit catalytic turnover.