Conservation of water molecules in an antibody-antigen interaction
Conservation of water molecules in an antibody-antigen interaction
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DOI：
10.1002/jmr.300080505
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发表时间：
1995-09-01
影响因子：
2.7
通讯作者：
Poljak, RJ
中科院分区：
文献类型：
--
作者：
Braden, BC;Fields, BA;Poljak, RJ
抗体抗原fvd1的溶剂化。通过对抗体D1.3的野生型Fv片段、5个游离溶菌酶、野生型Fv D1.3-溶菌酶复合物、5个与溶菌酶络合的Fv D1.3突变体和独特位体(Fv D1.3)-抗独特位体（Fv E5.2）复合物晶体结构中水分子的保存性研究来研究s -溶菌酶复合物。在an中，有99个水分子是野生型和突变型抗体溶菌酶复合物共有的。抗体-溶菌酶界面包括25个有序的溶剂分子，在野生型和突变型Fv d1.3 -溶菌酶复合物中是保守的，它们直接或通过其他水分子与抗体和抗原结合。除了为抗体-抗原相互作用提供氢键外，溶剂分子还填充了许多界面空腔。与游离fvd1.3和游离溶菌酶的x射线晶体结构比较表明，络合物中有20个保守的界面水与其中一个游离蛋白结合。在抗体-抗原界面上还发现了多达23个额外的水分子，但这些水分子不能桥接抗体和抗原，而且它们的温度因子远高于25个有序水分子。15个水分子被置换形成络合物，其中一些水分子被亲水性蛋白原子取代，5个水分子被添加到抗体-抗原界面形成络合物。虽然d1.3 -溶菌酶复合物的当前晶体模型并没有显示出在水活性降低时相互作用的物理化学研究中发现的结合水的增加，但25个有序的界面水为复合物的稳定性贡献了10个氢键的净收益。
The solvation of the antibody-antigen Fv D1.S-lysozyme complex is investigated through a study of the conservation of water molecules in crystal structures of the wild-type Fv fragment of antibody D1.3, 5 free lysozyme, the wild-type Fv D1.3-lysozyme complex, 5 Fv D1.3 mutants complexed with lysozyme and the crystal structure of an idiotope (Fv D1.3)-anti-idiotope (Fv E5.2) complex. In an, there are 99 water molecules common to the wild-type and mutant antibody-lysozyme complexes. The antibody-lysozyme interface includes 25 well-ordered solvent molecules, conserved among the wild-type and mutant Fv D1.3-lysozyme complexes, which are bound directly or through other water molecules to both antibody and antigen. In addition to contributing hydrogen bonds to the antibody-antigen interaction the solvent molecules fill many interface cavities. Comparison with x-ray crystal structures of free Fv D1.3 and free lysozyme shows that 20 of these conserved interface waters in the complex were bound to one of the free proteins. Up to 23 additional water molecules are also found in the antibody-antigen interface, however these waters do not bridge antibody and antigen and their temperature factors are much higher than those of the 25 well-ordered waters. Fifteen water molecules are displaced to form the complex, some of which are substituted by hydrophilic protein atoms, and 5 water molecules are added at the antibody-antigen interface with the formation of the complex. While the current crystal models of the D1.3-lysozyme complex do not demonstrate the increase in bound waters found in a physico-chemical study of the interaction at decreased water activities, the 25 well-ordered interface waters contribute a net gain of 10 hydrogen bonds to complex stability.