QM/MM modeling of compound I active species in cytochrome P450, Cytochrome c Peroxidase, and Ascorbate Peroxidase
QM/MM modeling of compound I active species in cytochrome P450, Cytochrome c Peroxidase, and Ascorbate Peroxidase
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DOI：
10.1002/jcc.20446
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发表时间：
2006-09-01
影响因子：
3
通讯作者：
Mulholland, Adrian J.
中科院分区：
文献类型：
--
作者：
Harvey, Jeremy N.;Bathelt, Christine M.;Mulholland, Adrian J.
QM/MM 计算提供了一种预测金属蛋白中金属中心电子结构的方法。两种血红素过氧化物酶，细胞色素 c 过氧化物酶 (CcP) 和抗坏血酸过氧化物酶 (APX)，具有结构上非常相似的活性位点，但具有电子结构非常不同的活性中间体。我们回顾了最近对这些系统的 QM/MM 计算，并提出了新的计算数据。我们的结果与实验非常吻合，表明电子结构的差异是由于一种蛋白质与另一种蛋白质的结构存在大量微小差异所致。我们还讨论了最近对细胞色素 P450 活性物质的 QM/MM 计算，其中发现电子结构对环境具有类似的敏感性。然而，这似乎并不能解释此类酶的不同药物代谢亚型的不同催化特性。 (c) 2006 年 Wiley 期刊公司
QM/MM calculations provide a means for predicting the electronic structure of the metal center in metalloproteins. Two heme peroxidases, Cytochrome c Peroxidase (CcP) and Ascorbate Peroxidase (APX), have a structurally very similar active site, yet have active intermediates with very different electronic structures. We review our recent QM/MM calculations on these systems, and present new computational data. Our results are in good agreement with experiment, and suggest that the difference in electronic structure is due to a large number of small differences in structure from one protein to another. We also discuss recent QM/MM calculations on the active species of cytochrome P450, in which a similar sensitivity of the electronic structure to the environment is found. However, this does not appear to explain different catalytic profiles of the different drug-metabolizing isoforms of this class of enzyme. (c) 2006 Wiley Periodicals, Inc.