Churg A K, Warshel A
Biochemistry. 1986 Apr 8;25(7):1675-81. doi: 10.1021/bi00355a035.
X-ray structural information provides the opportunity to explore quantitatively the relation between the microenvironments of heme proteins and their redox potentials. This can be done by considering the protein as a "solvent" for its redox center and calculating the difference between the electrostatic energy of the reduced and oxidized heme. Such calculations are presented here, applying the protein dipoles-Langevin dipoles (PDLD) model to cytochrome c. The calculations focus on an evaluation of the difference between the redox potentials of cytochrome c and the octapeptide-methionine complex formed by hydrolysis of cytochrome c. The corresponding difference (approximately 7 kcal/mol) is accounted for by the PDLD calculations. It is found that the protein provides basically a low dielectric environment for the heme, which destabilizes the oxidized heme (relative to its energy in water). The effect of the charged propionic acids on the heme is examined in a preliminary way. It is found that the negative charges of these groups are in a hydrophilic rather than a hydrophobic environment and that the protein-water system provides an effective high dielectric constant for their interaction with the heme. The dual nature of the dielectric effect of the cytochrome (a low dielectric constant for the self-energy of the heme and a high dielectric constant for charge-charge interactions) is discussed. The findings of this work are consistent with the difference between the folding energies of the reduced and oxidized cytochrome c.
X射线结构信息为定量探索血红素蛋白的微环境与其氧化还原电位之间的关系提供了契机。这可以通过将蛋白质视为其氧化还原中心的“溶剂”，并计算还原态和氧化态血红素的静电能之差来实现。本文进行了此类计算，将蛋白质偶极-朗之万偶极（PDLD）模型应用于细胞色素c。计算重点评估细胞色素c与细胞色素c水解形成的八肽-甲硫氨酸复合物的氧化还原电位之差。PDLD计算得出了相应的差值（约7千卡/摩尔）。研究发现，蛋白质基本上为血红素提供了一个低介电环境，这使得氧化态血红素不稳定（相对于其在水中的能量）。初步考察了带电荷的丙酸对血红素的影响。研究发现，这些基团的负电荷处于亲水性而非疏水性环境中，并且蛋白质-水系统为它们与血红素的相互作用提供了有效的高介电常数。讨论了细胞色素介电效应的双重性质（血红素自身能量的低介电常数和电荷-电荷相互作用的高介电常数）。这项工作的发现与还原态和氧化态细胞色素c的折叠能之差一致。
