Derat Etienne, Shaik Sason
Department of Organic Chemistry and the Lise Meitner-Minerva Center for Computational Quantum Chemistry, Hebrew University of Jerusalem, Givat Ram Campus, 91904 Jerusalem, Israel.
J Am Chem Soc. 2006 Oct 25;128(42):13940-9. doi: 10.1021/ja065058d.
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(*)(+)Fe(III)OH 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.
利用量子力学/分子力学计算方法研究了辣根过氧化物酶（邓福德，H.B.血红素过氧化物酶；威利-维克希：纽约，1999年）的活性物种化合物I和化合物II氧化天然底物（阿魏酸）的过程，以及该酶恢复到其静止状态的方式。结果与实验发现相符，并揭示了其他新特征。计算表明，这两个氧化过程均由质子耦合电子转移（PCET）步骤引发，在该步骤中，酶的活性物种仅作为电子转移伙伴参与，而整个质子转移事件则通过水分子（W402）在底物与His42残基之间传递。观察到的（亨里克森，A；史密斯，A.T.；加赫德，M.《生物化学杂志》1999年，274卷，35005 - 35011页）化合物I和化合物II对阿魏酸具有相似反应活性的原因是，化合物II的反应性异构体是迄今未观察到的、类似于化合物I的Por(*)(+)Fe(III)OH异构体。PCET机制表明，His42和W402是关键部分，它们决定了HRP酶的功能，并解释了其进行底物氧化的能力（普洛斯，T.L.过氧化物酶和细胞色素P450。见《卟啉手册》；卡迪什，K.M.，史密斯，K.M.，吉拉尔，R.编；学术出版社：纽约，2000年；第4卷，第189页）。鉴于这些结果，通过磁场操纵底物氧化的可能性是一个有趣的设想。
