细胞色素P450 2D6的T309V突变体中自旋态平衡的改变：一项光谱学和计算研究。
Altered spin state equilibrium in the T309V mutant of cytochrome P450 2D6: a spectroscopic and computational study.
作者信息
Bonifacio Alois, Groenhof André R, Keizers Peter H J, de Graaf Chris, Commandeur Jan N M, Vermeulen Nico P E, Ehlers Andreas W, Lammertsma Koop, Gooijer Cees, van der Zwan Gert
机构信息
Department of Chemistry and Pharmaceutical Sciences, Sections of Analytical Chemistry and Applied Spectroscopy (ACAS), Organic and Inorganic Chemistry and Molecular Toxicology, Vrije Universiteit, Amsterdam, The Netherlands.
出版信息
J Biol Inorg Chem. 2007 Jun;12(5):645-54. doi: 10.1007/s00775-007-0210-5. Epub 2007 Feb 23.
Cytochrome P450 2D6 (CYP2D6) is one of the most important cytochromes P450 in humans. Resonance Raman data from the T309V mutant of CYP2D6 show that the substitution of the conserved I-helix threonine situated in the enzyme's active site perturbs the heme spin equilibrium in favor of the six-coordinated low-spin species. A mechanistic hypothesis is introduced to explain the experimental observations, and its compatibility with the available structural and spectroscopic data is tested using quantum-mechanical density functional theory calculations on active-site models for both the CYP2D6 wild type and the T309V mutant.
细胞色素P450 2D6（CYP2D6）是人体内最重要的细胞色素P450之一。来自CYP2D6的T309V突变体的共振拉曼数据表明，位于酶活性位点的保守I-螺旋苏氨酸的取代扰乱了血红素自旋平衡，有利于六配位低自旋物种。引入了一个机理假设来解释实验观察结果，并使用对CYP2D6野生型和T309V突变体的活性位点模型进行的量子力学密度泛函理论计算，来测试其与现有结构和光谱数据的兼容性。
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