STABILITY AND SPECIFICITY OF PROTEIN-PROTEIN INTERACTIONS - CASE OF TRYPSIN-TRYPSIN INHIBITOR COMPLEXES
STABILITY AND SPECIFICITY OF PROTEIN-PROTEIN INTERACTIONS - CASE OF TRYPSIN-TRYPSIN INHIBITOR COMPLEXES
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DOI：
10.1016/s0022-2836(76)80148-9
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发表时间：
1976-01-01
影响因子：
5.6
通讯作者：
CHOTHIA, C
中科院分区：
文献类型：
--
作者：
JANIN, J;CHOTHIA, C
胰蛋白酶与胰蛋白酶抑制剂和大豆胰蛋白酶抑制剂的晶体复合物的原子坐标被用来计算包埋在复合物中的蛋白质表面积。这给出了解离自由能的疏水贡献值，该值与水可接近的表面积直接相关。大部分被掩埋的表面积由十几个胰蛋白酶氨基酸残基和抑制剂的结合环提供。这些残基形成紧密堆积的界面，尽管在两种复合物中的堆积是完全不同的。在复合物形成时发生的平移熵和旋转熵的大损失由由于溶剂可接近的较小表面积引起的疏水自由能平衡。虽然与疏水性相比，极性相互作用对解离自由能的贡献很小，但形成紧密堆积界面的能力（极性原子适当定位以产生氢键）在胰蛋白酶特异性中起着重要作用。
Atomic co-ordinates of the crystalline complexes of trypsin with pancreatic trypsin inhibitor and with soybean trypsin inhibitor were used to calculate the protein surface area buried in the complexes. This gives a value of the hydrophobic contribution to the free energy of dissociation, a quantity directly related to the surface area accessible to water. Most of the buried surface area is provided by a dozen trypsin amino acid residues and by the binding loops of the inhibitors. These residues form close-packed interfaces, though the packing is quite different in the two complexes. The large loss of translational and rotational entropy which occurs upon complex formation is balanced by the hydrophobic free energy due to the smaller surface area accessible to the solvent. While the contribution of polar interactions to the free energy of dissociation is small compared to that of hydrophobicity, the ability to form close-packed interfaces, with the polar atoms properly positioned to give hydrogen bonds, plays an essential part in trypsin specificity.