Xiao L, Honig B
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, 10032, USA.
J Mol Biol. 1999 Jun 25;289(5):1435-44. doi: 10.1006/jmbi.1999.2810.
Electrostatic contributions to the folding free energy of several hyperthermophilic proteins and their mesophilic homologs are calculated. In all the cases studied, electrostatic interactions are more favorable in the hyperthermophilic proteins. The electrostatic free energy is found not to be correlated with the number of ionizable amino acid residues, ion pairs or ion pair networks in a protein, but rather depends on the location of these groups within the protein structure. Moreover, due to the large free energy cost associated with burying charged groups, buried ion pairs are found to be destabilizing unless they undergo favorable interactions with additional polar groups, including other ion pairs. The latter case involves the formation of stabilizing ion pair networks as is observed in a number of proteins. Ion pairs located on the protein surface also provide stabilizing interactions in a number of cases. Taken together, our results suggest that many hyperthermophilic proteins enhance electrostatic interactions through the optimum placement of charged amino acid residues within the protein structure, although different design strategies are used in different cases. Other physical mechanisms are also likely to contribute, however optimizing electrostatic interactions offers a simple means of enhancing stability without disrupting the core residues characteristic of different protein families.
计算了静电作用对几种嗜热蛋白质及其嗜温同源物折叠自由能的贡献。在所研究的所有情况下，嗜热蛋白质中的静电相互作用更为有利。发现静电自由能与蛋白质中可电离氨基酸残基、离子对或离子对网络的数量无关，而是取决于这些基团在蛋白质结构中的位置。此外，由于埋藏带电基团会产生巨大的自由能成本，除非埋藏的离子对与包括其他离子对在内的额外极性基团发生有利的相互作用，否则它们会使蛋白质不稳定。后一种情况涉及形成稳定的离子对网络，这在许多蛋白质中都有观察到。在许多情况下，位于蛋白质表面的离子对也提供稳定的相互作用。综上所述，我们的结果表明，许多嗜热蛋白质通过在蛋白质结构中最佳放置带电氨基酸残基来增强静电相互作用，尽管在不同情况下使用了不同的设计策略。然而，其他物理机制也可能起作用，优化静电相互作用提供了一种增强稳定性而不破坏不同蛋白质家族特征性核心残基的简单方法。
