Contribution of amino acid substitutions at two different interior positions to the conformational stability of human lysozyme
Contribution of amino acid substitutions at two different interior positions to the conformational stability of human lysozyme
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DOI：
10.1093/protein/12.10.841
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发表时间：
1999-10-01
期刊：
影响因子：
--
通讯作者：
Yutani, K
中科院分区：
文献类型：
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作者：
Funahashi, J;Takano, K;Yutani, K
为了阐明蛋白质结构变化与热力学稳定性之间的相关关系，研究了一系列在两个埋藏位置（Ile 56和Ile 59）修饰的突变型人溶菌酶。用量热法和X射线晶体学方法研究了它们的变性热力学参数和晶体结构。由于取代而引起的稳定性变化与取代残基的疏水性变化呈线性相关，在每个突变位点具有不同的斜率。然而，每个突变体的稳定性被认为是由一个独特的方程，涉及从突变体结构计算的物理性质。通过将在不同位置取代的突变体人溶菌酶的当前和先前的稳定性数据拟合到方程，发现碳原子的疏水性以及氮原子和中性氧原子的疏水性的大小分别为0.178和-0.013 kJ/mol.埃（2）。还发现，长度为3.0埃的氢键对蛋白质稳定性的贡献为5.1 kJ/mol，新引入的水分子的熵损失为7.8 kJ/mol。
To elucidate correlative relationships between structural change and thermodynamic stability in proteins, a series of mutant human lysozymes modified at two buried positions (Ile56 and Ile59) were examined. Their thermodynamic parameters of denaturation and crystal structures were studied by calorimetry and X-ray crystallography, The mutants at positions 56 and 59 exhibited different responses to a series of amino acid substitutions. The changes in stability due to substitutions showed a linear correlation with changes in hydrophobicity of substituted residues, having different slopes at each mutation site. However, the stability of each mutant was found to be represented by a unique equation involving physical properties calculated from mutant structures. By fitting present and previous stability data for mutant human lysozymes substituted at various positions to the equation, the magnitudes of the hydrophobicity of a carbon atom and the hydrophobicity of nitrogen and neutral oxygen atoms were found to be 0.178 and -0.013 kJ/mol.Angstrom(2), respectively. It was also found that the contribution of a hydrogen bond with a length of 3.0 Angstrom to protein stability was 5.1 kJ/mol and the entropy loss of newly introduction of a water molecules was 7.8 kJ/mol.