Structural insights revealed by crystal structures of CYP76AH1 and CYP76AH1 in complex with its natural substrate
Structural insights revealed by crystal structures of CYP76AH1 and CYP76AH1 in complex with its natural substrate
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CYP76AH1 和 CYP76AH1 与其天然底物复合物的晶体结构揭示了结构见解
DOI：
10.1016/j.bbrc.2021.10.004
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发表时间：
2021-10-25
影响因子：
3.1
通讯作者：
Chang, Zhenzhan
中科院分区：
文献类型：
--
作者：
Shi, Chao;Gu, Mingyue;Chang, Zhenzhan
丹参酮类化合物是著名的天然产物，具有抗心脏病等多种药理活性，而丹参酮类化合物的生物合成途径中的关键酶是CYP76AH1。CYP76AH1是一种典型的植物细胞色素P450酶，其催化机制尚不清楚。真核生物P450酶的结构测定极具挑战性。最近，我们解决了CYP76AH1和CYP76AH1与其天然底物miltiradiene的复合物的晶体结构。CYP76AH1与米替雷烯复合的结构是第一个与天然底物复合的植物细胞色素P450结构。这些研究揭示了一种独特的氨基酸残基阵列模式，这可能在定向和稳定催化底物方面发挥重要作用。这项工作将提供结构的见解CYP76AH1和相关的P450和基础，有效地提高丹参酮的合成生物学技术生产。(c)2021爱思唯尔公司All rights reserved.
CYP76AH1 is the key enzyme in the biosynthesis pathway of tanshinones in Salvia miltiorrhiza, which are famous natural products with activities against various heart diseases and others. CYP76AH1 is a membrane-associated typical plant class II cytochrome P450 enzyme and its catalytic mechanism has not to be clearly elucidated. Structural determination of eukaryotic P450 enzymes is extremely challenging. Recently, we solved the crystal structures of CYP76AH1 and CYP76AH1 in complex with its natural substrate miltiradiene. The structure of CYP76AH1 complexed with miltiradiene is the first plant cytochrome P450 structure in complex with natural substrate. The studies revealed a unique array pattern of amino acid residues, which may play an important role in orienting and stabilizing the substrate for catalysis. This work would provide structural insights into CYP76AH1 and related P450s and the basis to efficiently improve tanshinone production by synthetic biology techniques. (c) 2021 Elsevier Inc. All rights reserved.