A single-site mutation (F429H) converts the enzyme CYP 2B4 into a heme oxygenase: a QM/MM study.
A single-site mutation (F429H) converts the enzyme CYP 2B4 into a heme oxygenase: a QM/MM study.
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单位点突变 (F429H) 将 CYP 2B4 酶转化为血红素加氧酶：一项 QM/MM 研究。
DOI：
10.1021/ja211905e
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发表时间：
2012
影响因子：
15
通讯作者：
Shaik,Sason
中科院分区：
文献类型：
--
作者：
Usharani,Dandamudi;Zazza,Costantino;Lai,Wenzhen;Chourasia,Mukesh;Waskell,Lucy;Shaik,Sason
通过对(Fe3+OOH)−中间体O-OH键激活的量子力学/分子力学计算，探索了由单个残基Phe429突变引起的细胞色素P450 (CYP) 2B4酶的失活。发现CYP 2B4的F429H突变体发生的是co - oh键的均质分裂，而不是异质分裂。因此，突变体获得了血红素加氧酶的以下特征：(a) His429向半胱氨酸配体提供额外的NH—S氢键，结合底物的存在，延缓了异裂解裂解，并引起O-OH的同裂解裂解；(b) Thr302/水簇定向新生OH•，并确保有效的中位羟基化。
The intriguing deactivation of the cytochrome P450 (CYP) 2B4 enzyme induced by mutation of a single residue, Phe429 to His, is explored by quantum mechanical/molecular mechanical calculations of the O–OH bond activation of the (Fe3+OOH)−intermediate. It is found that the F429H mutant of CYP 2B4 undergoeshomolytic instead of heterolyticO–OH bond cleavage. Thus, the mutant acquires the following characteristics of a heme oxygenase enzyme: (a) donation by His429 of an additional NH---S H-bond to the cysteine ligand combined with the presence of the substrate retards the heterolytic cleavage and gives rise to homolytic O–OH cleavage, and (b) the Thr302/water cluster orients nascent OH•and ensures efficient meso hydroxylation.