Trinuclear Metal Clusters in Catalysis by Terpenoid Synthases.
Trinuclear Metal Clusters in Catalysis by Terpenoid Synthases.
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DOI：
10.1351/pac-con-09-09-37
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Christianson DW
中科院分区：
文献类型：
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作者：
Aaron JA;Christianson DW
萜类合成酶是一种普遍存在的酶，它催化形成结构和立体化学上不同的异戊二烯类天然产物。细菌、真菌、原生动物、植物和动物中的许多异戊二烯偶联酶和萜类环酶共享I类萜类合成酶折叠。尽管这些例子中的氨基酸序列同源性一般较低，但I类萜类合成酶包含保守的金属结合基序，这些基序与三核金属簇配位。该簇不仅用于结合和定向前催化米氏络合物中的柔性异戊二烯底物，而且还触发二磷酸离开基团产生碳正离子，从而启动催化。另外，保守的氢键供体有助于金属簇的这一功能。晶体结构分析表明，在所有已知结构的I类萜类合成酶中，催化萜类合成酶所需的三种金属离子的星座大体相同。
Terpenoid synthases are ubiquitous enzymes that catalyze the formation of structurally and stereochemically diverse isoprenoid natural products. Many isoprenoid coupling enzymes and terpenoid cyclases from bacteria, fungi, protists, plants, and animals share the class I terpenoid synthase fold. Despite generally low amino acid sequence identity among these examples, class I terpenoid synthases contain conserved metal binding motifs that coordinate to a trinuclear metal cluster. This cluster not only serves to bind and orient the flexible isoprenoid substrate in the precatalytic Michaelis complex, but it also triggers the departure of the diphosphate leaving group to generate a carbocation that initiates catalysis. Additional conserved hydrogen bond donors assist the metal cluster in this function. Crystal structure analysis reveals that the constellation of three metal ions required for terpenoid synthase catalysis is generally identical among all class I terpenoid synthases of known structure.