Relevant Anion-π Interactions in Biological Systems: The Case of Urate Oxidase
Relevant Anion-π Interactions in Biological Systems: The Case of Urate Oxidase
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DOI：
10.1002/anie.201005635
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发表时间：
2011-01-01
影响因子：
16.6
通讯作者：
Deya, Pere M.
中科院分区：
文献类型：
--
作者：
Estarellas, Carolina;Frontera, Antonio;Deya, Pere M.
超分子化学涉及分子间非共价相互作用的智能利用。所有的生物系统都是基于这些令人印象深刻的有效相互作用。[1]预先设计的结合中心之间的相互作用可以导致高度有序的分子系统中的复杂功能，这是超分子化学的一个基本方面。[2]阴离子-π相互作用的重要性已被广泛认识[3]，并导致了许多理论和实验研究。[4]一些开创性的理论研究表明，这些相互作用在能量上是有利的。[5]阴离子-π相互作用正在引起人们的极大兴趣;例如，Matile及其同事已经报道了基于阴离子-π相互作用的显着合成离子通道。[6]然而，文献中缺乏可能在酶中起关键作用的阴离子-π相互作用的明确证据。证明这种非共价相互作用的重要性的最终步骤是证明它在生物系统中的关键作用。[7]在这些实例中，相关阴离子-π相互作用存在于尿酸氧化酶的活性位点中，并且导致与抑制酶活性的底物（尿酸）的相互作用或与抑制剂（8-氮杂黄嘌呤）的相互作用。此外，利用量子力学计算，我们证明了在固态中观察到的相互作用是相关的，积极有利的。尿酸氧化酶（UOX，EC 1.7. 3.3)是一种同源四聚体无辅因子酶，在分子氧存在下，通过一种特异性酶级联反应催化尿酸（URC）羟基化为（S）-尿囊素，
Supramolecular chemistry involves the intelligent utilization of noncovalent interactions between molecules. All biological systems are based on these impressively efficient interactions.[1] Interactions between predesigned binding centers can lead to complex functions in highly organized molecular systems, which is one fundamental aspect of supramolecular chemistry.[2] The importance of anion–π interactions has been widely recognized [3] and has led to many theoretical and experimental investigations.[4] Several pioneering theoretical studies revealed that these interactions are energetically favorable.[5] Anion–π interactions are gaining significant interest; for instance, Matile and co-workers have reported remarkable synthetic ion channels based on anion–π interactions.[6] However, clear evidence of anion–π interactions that likely play a key role in enzymes is lacking in the literature. The ultimate step to prove the importance of this noncovalent interaction is to demonstrate its crucial role in a biological system.Herein we report several selected examples retrieved from the Protein Data Bank (PDB).[7] In these examples, relevant anion–π interactions are present in the active site of the urate oxidase enzyme, and lead either to interactions with the substrate (uric acid) that inhibits the enzymatic activity or to interactions with the inhibitor (8-azaxanthine). In addition, taking advantage of quantum mechanical calculations, we demonstrate that the interactions observed in the solid state are relevant and energetically favorable. Urate oxidase (UOX, EC 1.7. 3.3) is a homotetrameric cofactorless enzyme, which in the presence of molecular oxygen catalyzes the hydroxylation of uric acid (URC) to (S)-allantoin through a specific enzymatic cascade that involves