Direct Observation of an Enamine Intermediate in Amine Catalysis
Direct Observation of an Enamine Intermediate in Amine Catalysis
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DOI：
10.1021/ja907271a
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发表时间：
2009-12-30
影响因子：
15
通讯作者：
Wilson, Ian A.
中科院分区：
文献类型：
--
作者：
Zhu, Xueyong;Tanaka, Fujie;Wilson, Ian A.
烯胺中间体被认为是生物催化剂如醛缩酶和小分子胺有机催化剂的中心特征。尽管对天然存在的醛缩酶进行了数十年的研究，并且最近对设计的醛缩酶抗体和有机催化剂进行了研究，但烯胺中间体的直接结构观察已被证明是罕见的。在此，我们报告了在与1，3-二酮衍生物复合的醛缩酶抗体33F12的晶体结构中观察到稳定的烯胺中间体。这种烯胺复合物结构提供了强有力的证据，表明这种催化抗体的疏水环境中的胺催化所必需的残基比天然醛缩酶推测的少，并且应该用于指导未来的研究，旨在合理设计这些类型的催化剂以及有机催化剂。事实上，蛋白质中的烯胺催化可能比以前想象的更简单。
An enamine intermediate is believed to be the central feature of biological catalysts, such as aldolases and small molecule amine organocatalysts. Despite decades of investigation of naturally occurring aldolase enzymes and recent studies on designed aldolase antibodies and organocatalysts, direct structural observation of an enamine intermediate has proven to be rare. Herein, we report the observation of a stable enamine intermediate in the crystal structure of an aldolase antibody 33F12 in complex with a 1,3-diketone derivative. This enamine complex structure provides strong evidence that fewer residues are essential for amine catalysis within the hydrophobic environments of this catalytic antibody than speculated for natural aldolase enzymes and should serve to guide future studies aimed at the rational design of these types of catalysts, as well as organocatalysts. Indeed, enamine catalysis in proteins might be more simplistic than previously imagined.