Structural Insights into a Flavin-Dependent [4+2] Cyclase that Catalyzes trans-Decalin Formation in Pyrroindomycin Biosynthesis
Structural Insights into a Flavin-Dependent [4+2] Cyclase that Catalyzes trans-Decalin Formation in Pyrroindomycin Biosynthesis
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吡咯吲哚霉素生物合成中催化反十氢萘形成的黄素依赖性 [4 2] 环化酶的结构见解
DOI：
10.1016/j.chembiol.2018.03.007
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发表时间：
2018
影响因子：
8.6
通讯作者：
Wen Liu
中科院分区：
文献类型：
--
作者：
Qingfei Zheng;Yukang Gong;Yujiao Guo;Zhixiong Zhao;Zhuhua Wu;Zixuan Zhou;D;an Chen;Lifeng Pan;Wen Liu
在这里，我们提供了结构的见解PyrE 3，黄素依赖性[4 + 2]环化酶，催化反式萘烷形成的生物合成吡咯吲哚霉素。PyrE 3与对羟基苯甲酸羟化酶（pHBH）-折叠单加氧酶家族成员的结构/结构域相似，具有黄素腺嘌呤二核苷酸（FAD）-结合结构域、中间结构域和C-末端硫氧还蛋白样结构域。FAD结合结构域形成蛋白质结构的中心枢纽，并以pHBH折叠家族单加氧酶的“闭合”构象与FAD结合，所述pHBH折叠家族单加氧酶以其高度动态催化过程而闻名。FAD在PyrE 3中起着重要的结构作用，在那里它是顺从的氧化还原变化;然而，氧化还原变化对[4 + 2]环化活性几乎没有影响。PyrE 3似乎选择性地容纳一个高正电荷口袋中的含四酸酯的线性多烯中间体，该口袋位于FAD结合结构域和中间结构域之间的界面处，并且可能通过内选择性[4 + 2]过渡态加速反式十氢萘的形成。
Here, we provide structural insights into PyrE3, a flavin-dependent [4 + 2] cyclase that catalyzestrans-decalin formation in the biosynthesis of pyrroindomycins. PyrE3 shares an architecture/domain organization head-to-tail similarity with the members of the family ofpara-hydroxybenzoate hydroxylase (pHBH)-fold monooxygenases, and possesses a flavin adenine dinucleotide (FAD)-binding domain, a middle domain, and a C-terminal thioredoxin-like domain. The FAD-binding domain forms a central hub of the protein structure, and binds with FAD in a "closed" conformation of pHBH-fold family monooxygenases known for their highly dynamic catalytic processes. FAD plays an essential structural role in PyrE3, where it is amenable to redox change; however, redox change has little effect on [4 + 2] cyclization activity. PyrE3 appears to selectively accommodate a tetramate-containing, linear polyene intermediate in a highly positively charged pocket, which is located at the interface between the FAD-binding domain and the middle domain, and can acceleratetrans-decalin formation likely through anendo-selective [4 + 2] transition state.