The enolase superfamily: A general strategy for enzyme-catalyzed abstraction of the alpha-protons of carboxylic acids
The enolase superfamily: A general strategy for enzyme-catalyzed abstraction of the alpha-protons of carboxylic acids
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DOI：
10.1021/bi9616413
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发表时间：
1996-12-24
期刊：
影响因子：
2.9
通讯作者：
Gerlt, JA
中科院分区：
文献类型：
--
作者：
Babbitt, PC;Hasson, MS;Gerlt, JA
我们发现了酶的超家族，其能够催化羧酸α-普罗顿的抽象以形成氧化中间体的能力。尽管这些酶催化的每种反应都是由这个共同的步骤引发的，但它们的总体反应（包括种族化，水的β-省β-释放，氨基β释放和环异构化）以及立体化学后果（VS vs and） - 淘汰反应是多种多样的。这些蛋白质之间的序列和结构相似性的分析表明，它们的所有化学反应都是由通过进化修饰的常见活性位点体系结构介导的，以允许通过不同的整体机制将烯醇中间体在其各自的活性位点分配到不同的产物。所有这些酶都保留了催化质子抽象热力学困难步骤的能力。 These homologous proteins, designated the ''enolase superfamily'', include enolase as well as more metabolically specialized enzymes: mandelate racemase, galactonate dehydratase, glucarate dehydratase, muconate-lactonizing enzymes, N-acylamino acid racemase, beta-methylaspartate ammonia-lyase,和O-核苯基苯甲酸酯合酶。超家族中结构功能关系的比较分析表明，羧基 - 膦醇丙酮酸合酶是超家族的另一个成员，并不能催化文献中提出的反应，而是催化烯醇酶样反应。超家族中建立的和推导的结构功能关系允许这样的预测，即尚未分配尚未分配催化功能的家族中其他明显的成员也将进行化学，涉及羧酸α-普罗顿的抽象。
We have discovered a superfamily of enzymes related by their ability to catalyze the abstraction of the alpha-proton of a carboxylic acid to form an enolic intermediate. Although each reaction catalyzed by these enzymes is initiated by this common step, their overall reactions (including racemization, beta-elimination of water, beta-elimination of ammonia, and cycloisomerization) as well as the stereochemical consequences (syn vs anti) of the beta-elimination reactions are diverse. Analysis of sequence and structural similarities among these proteins suggests that all of their chemical reactions are mediated by a common active site architecture modified through evolution to allow the enolic intermediates to partition to different products in their respective active sites via different overall mechanisms. All of these enzymes retain the ability to catalyze the thermodynamically difficult step of proton abstraction. These homologous proteins, designated the ''enolase superfamily'', include enolase as well as more metabolically specialized enzymes: mandelate racemase, galactonate dehydratase, glucarate dehydratase, muconate-lactonizing enzymes, N-acylamino acid racemase, beta-methylaspartate ammonia-lyase, and o-succinylbenzoate synthase. Comparative analysis of structure-function relationships within the superfamily suggests that carboxy-phosphonoenolpyruvate synthase, another member of the superfamily, does not catalyze the reaction proposed in the literature but catalyzes an enolase-like reaction instead. The established and deduced structure-function relationships in the superfamily allow the prediction that other apparent members of the family for which no catalytic functions have yet been assigned will also perform chemistry involving abstraction of the alpha-protons of carboxylic acids.