An efficient proton-coupled electron-transfer process during oxidation of ferulic acid by horseradish peroxidase: Coming full cycle
An efficient proton-coupled electron-transfer process during oxidation of ferulic acid by horseradish peroxidase: Coming full cycle
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DOI：
10.1021/ja065058d
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发表时间：
2006-10-25
影响因子：
15
通讯作者：
Shaik, Sason
中科院分区：
文献类型：
--
作者：
Derat, Etienne;Shaik, Sason
利用量子力学/分子力学计算来研究辣根过氧化物酶（Dunford，H.B.血红素过氧化物酶；Wiley-VCH：纽约，1999）、化合物I和化合物II的活性物质氧化天然底物（阿魏酸）的过程，以及酶返回其静止状态的方式。结果与实验结果相符，并揭示了其他新特征。计算表明，这两个氧化过程都是由质子耦合电子转移 (PCET) 步骤启动，其中酶的活性物质仅作为电子转移伙伴参与，而整个质子转移事件通过水分子 (W402) 在底物和 His42 残基之间进行传递。观察到（Henriksen，A；Smith，A.T.；Gajhede，M.J.Biol.Chem.1999,274,35005-35011）化合物I和化合物II对阿魏酸的相似反应性的原因是，化合物II的反应性异构体是迄今为止未观察到的与化合物I相似的中心点+(FeOH)-O-III异构体。 PCET 机制揭示 His42 和 W402 是关键部分，它们决定 HRP 酶的功能并解释其执行底物氧化的能力（Poulos, T. L. 过氧化物酶和细胞色素 P450。卟啉手册；Kadish, K. M.、Smith, K. M.、Guilard, R., Eds.；学术出版社：纽约，2000 年；第 4 卷，第 4 页） 189）。从结果来看，通过磁场操纵基质氧化的可能性是一个有趣的可能性。
Quantum mechanics/ molecular mechanics calculations were utilized to study the process of oxidation of a native substrate (ferulic acid) by the active species of horseradish peroxidase (Dunford, H. B. Heme Peroxidases;Wiley-VCH: New York, 1999), Compound I and Compound II, and the manner by which the enzyme returns to its resting state. The results match experimental findings and reveal additional novel features. The calculations demonstrate that both oxidation processes are initiated by a proton-coupled electron-transfer (PCET) step, in which the active species of the enzyme participate only as electron-transfer partners, while the entire proton-transfer event is being relayed from the substrate to and from the His42 residue by a water molecule (W402). The reason for the observed (Henriksen, A; Smith, A. T.; Gajhede, M. J. Biol. Chem. 1999, 274, 35005-35011) similar reactivities of Compound I and Compound II toward ferulic acid is that the reactive isomer of Compound II is the, hitherto unobserved, Por center dot+(FeOH)-O-III isomer that resembles Compound I. The PCET mechanism reveals that His42 and W402 are crucial moieties and they determine the function of the HRP enzyme and account for its ability to perform substrate oxidation (Poulos, T. L. Peroxidases and Cytochrome P450. In The Porphyrin Handbook; Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic Press: New York, 2000; Vol. 4, pp 189). In view of the results, the possibility of manipulating substrate oxidation by magnetic fields is an intriguing possibility.