Switching on a Nontraditional Enzymatic Base-Deprotonation by Serine in the ent-Kaurene Synthase from Bradyrhizobium japonicum
Switching on a Nontraditional Enzymatic Base-Deprotonation by Serine in the ent-Kaurene Synthase from Bradyrhizobium japonicum
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DOI：
10.1021/acscatal.9b02783
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发表时间：
2019-10-01
期刊：
影响因子：
12.9
通讯作者：
Peters, Reuben J.
中科院分区：
文献类型：
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作者：
Jia, Meirong;Zhang, Yue;Peters, Reuben J.
萜烯合酶经常催化复杂的碳阳离子级联反应。先前已经表明，涉及用丝氨酸或苏氨酸替换关键脂肪族残基的单残基转换可以“短路”此类反应，这些反应被认为是通过中间碳阳离子的偶极稳定间接起作用。在来自日本慢生根瘤菌的结构特征对映贝壳杉烯合酶中发现了类似的开关。最近开发的萜烯合酶计算方法 TerDockin 的应用令人惊讶地表明引入的丝氨酸羟基作为催化碱的直接作用。值得注意的是，该模型提出了对先前结果的另一种解释以及更普遍地重新设计萜烯合酶活性的潜在途径。
Terpene synthases often catalyze complex carbocation cascade reactions. It has been previously shown that single-residue switches involving replacement of a key aliphatic residue with serine or threonine can "short-circuit" such reactions that are presumed to act indirectly via dipole stabilization of intermediate carbocations. Here a similar switch was found in the structurally characterized ent-kaurene synthase from Bradyrhizobium japonicum. Application of a recently developed computational approach to terpene synthases, TerDockin, surprisingly indicates direct action of the introduced serine hydroxyl as a catalytic base. Notably, this model suggests an alternative interpretation of previous results and potential routes toward reengineering terpene synthase activity more generally.