Sugita Yuji, Miyashita Naoyuki, Ikeguchi Mitsunori, Kidera Akinori, Toyoshima Chikashi
Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-0032, Japan.
J Am Chem Soc. 2005 May 4;127(17):6150-1. doi: 10.1021/ja0427505.
The ionization states of the acidic residues around the Ca2+-binding sites of sarcoplasmic reticulum Ca2+ ATPase are studied by continuum electrostatic calculations and all-atom molecular dynamics simulations with explicit solvent and phospholipids. The two methods consistently indicate that Glu58 and Glu908 are protonated at neutral pH. The Ca2+ coordination and the H-bonds formed by the protonation of Glu58 and Glu908 are stable in an MD simulation, whereas the H-bonds are disrupted and the Ca2+ coordination geometry is severely altered in another simulation treating these residues unprotonated. The results clearly indicate that the H-bonds formed by protonation of Glu58 and Glu908 provide extra stability for the Ca2+-binding sites of Ca2+ ATPase.
通过连续静电计算以及含明确溶剂和磷脂的全原子分子动力学模拟，研究了肌浆网Ca2+ - ATP酶Ca2+结合位点周围酸性残基的电离状态。这两种方法一致表明，在中性pH条件下，Glu58和Glu908处于质子化状态。在分子动力学模拟中，由Glu58和Glu908质子化形成的Ca2+配位和氢键是稳定的，而在另一个将这些残基视为未质子化的模拟中，氢键被破坏，Ca2+配位几何结构严重改变。结果清楚地表明，Glu58和Glu908质子化形成的氢键为Ca2+ - ATP酶的Ca2+结合位点提供了额外的稳定性。
