Density Functional and Electrostatic Calculations of Manganese Superoxide Dismutase Active Site Complexes in Protein Environments.
Density Functional and Electrostatic Calculations of Manganese Superoxide Dismutase Active Site Complexes in Protein Environments.
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DOI：
10.1021/ic980731o
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发表时间：
1999-02
影响因子：
4.6
通讯作者：
Jian Li;C. Fisher;R. Konečný;D. Bashford;Louis Noodleman
中科院分区：
文献类型：
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作者：
Jian Li;C. Fisher;R. Konečný;D. Bashford;Louis Noodleman
密度泛函和静电方法已用于计算活性位点几何形状和锰超氧化物歧化酶（MnSOD）的氧化还原电位。最初的活性位点簇是通过仅包含第一壳层侧链配体而构建的，然后通过第二壳层配体进行增强。还原复合物的密度泛函优化的 Mn-配体键长总体上与蛋白质晶体学数据相当好；然而，对于氧化的活性位点簇，计算出的 Mn-OH 距离存在较大偏差。我们的计算表明，这种偏差可归因于 X 射线晶体学研究中氧化蛋白质的氧化还原异质性。通过半宏观静电模型处理蛋白质环境和溶剂体积来计算氧化还原电位。蛋白质结构取自嗜热栖热菌酶。随着活性位点簇模型尺寸的增加，计算出的耦合氧化还原电位向实验值收敛，最终计算值为+0.06 V，而嗜热脂肪芽孢杆菌和大肠杆菌酶的实验值分别为+0.26 V和+0.31 V。使用能量分解方案，分析了第二壳配体以及蛋白质和反应场的影响。
Density functional and electrostatic methods have been applied to calculate active site geometries and the redox potential of manganese superoxide dismutase (MnSOD). The initial active site clusters were built up by including only first-shell side chain ligands and then augmented by second-shell ligands. The density functional optimized Mn-ligand bond lengths for the reduced complexes in general compared fairly well with protein crystallography data; however, large deviations for calculated Mn-OH distances were found for the oxidized active site clusters. Our calculations suggest that this deviation can be attributed to the redox heterogeneity of the oxidized protein in X-ray crystallography studies. The redox potential was calculated by treating the protein environment and the solvent bulk by a semimacroscopic electrostatic model. The protein structures were taken from the Thermus thermophilus enzyme. The calculated coupled redox potentials converge toward experimental values with increasing size of the active site cluster models, and the final calculated value was +0.06 V, compared to experimental values of +0.26 V determined for Bacillus stearothermophilus and +0.31 V in Escherichia coli enzymes. Using an energy decomposition scheme, the effects of the second-shell ligands and the protein and reaction fields have been analyzed.