Böhm G, Jaenicke R
Institut für Biophysik und Physikalische Biochemie, Universität Regensburg, Germany.
Protein Eng. 1994 Feb;7(2):213-20. doi: 10.1093/protein/7.2.213.
'Halophilic adaptation' of proteins, i.e. the requirement for high concentrations of monovalent ions for thermodynamic stability of proteins from halophilic organisms, is not fully understood. In this work, an explanation for the halophilic behavior of dihydrofolate reductase (h-DHFR) from Halobacterium volcanii is attempted, based on a model structure derived from comparative modeling to dihydrofolate reductase from Escherichia coli. The model structure of h-DHFR shows an unique asymmetrical charge distribution over the protein surface, with positively charged amino acids centered around the active site and negative charges on the opposite side of the enzyme. This particular charge distribution and the correlated molecular dipole are functionally relevant. The negative charges on the surface form clusters which are shielded at high salt concentrations; at low salt, they repulse each other, thus destabilizing the protein. Results are in accordance with denaturation data and, thus, provide an explanation for the exceptional stability properties of h-DHFR.
蛋白质的“嗜盐适应性”，即嗜盐生物的蛋白质热力学稳定性需要高浓度单价离子，目前尚未完全理解。在这项工作中，基于通过比较建模从大肠杆菌二氢叶酸还原酶推导得到的模型结构，尝试对火山嗜盐菌二氢叶酸还原酶（h-DHFR）的嗜盐行为作出解释。h-DHFR的模型结构显示出蛋白质表面独特的不对称电荷分布，带正电荷的氨基酸集中在活性位点周围，而酶的另一侧则带负电荷。这种特定的电荷分布和相关的分子偶极在功能上具有相关性。表面的负电荷形成簇，在高盐浓度下被屏蔽；在低盐浓度下，它们相互排斥，从而使蛋白质不稳定。结果与变性数据一致，因此为h-DHFR的特殊稳定性特性提供了解释。
