Tulinsky A, Mavridis I, Mann R F
J Biol Chem. 1978 Feb 25;253(4):1074-8.
Three-dimensional 2.8 A resolution x-ray crystallographic studies show that toluenesulfonamide and pipsylamide bind isomorphously in the aromatic specificity binding site of alpha-chymotrypsin. However, their orientation differs by about 90 degrees from that usually associated with substrate-like molecules, suggesting a nonproductive binding mode. A secondary binding site is also operative in one molecule of the dimer of the pipsylamide derivative and it is located some 22 A from the active site; however, this site is not operative in the toluenesulfonamide derivative. Binding of toluenesulfonamide and pipsylamide in the specificity site occurs without inducing any significant changes in the native enzyme structure, in contrast to the behavior observed upon tosylation or upon transition state analogue binding of phenylethaneboronic acid. The structural changes accompanying the formation of the latter derivatives are generally asymmetric with respect to the dimeric structure of alpha-chymotrypsin and are generally confined to the binding domain or cylinder 2 of the enzyme (sequence greater than 122). These changes are displayed in a new way via diagonal distance map representation.
三维2.8埃分辨率的X射线晶体学研究表明，甲苯磺酰胺和对甲苯磺酰胺在α-胰凝乳蛋白酶的芳香族特异性结合位点同晶型结合。然而，它们的取向与通常与底物样分子相关的取向相差约90度，表明存在非生产性结合模式。在对甲苯磺酰胺衍生物二聚体的一个分子中，二级结合位点也起作用，它位于距活性位点约22埃处；然而，该位点在甲苯磺酰胺衍生物中不起作用。与甲苯磺酰化或苯乙硼酸过渡态类似物结合时观察到的行为相反，甲苯磺酰胺和对甲苯磺酰胺在特异性位点的结合不会引起天然酶结构的任何显著变化。伴随后一种衍生物形成的结构变化通常相对于α-胰凝乳蛋白酶的二聚体结构是不对称的，并且通常局限于酶的结合结构域或圆柱2（序列大于122）。这些变化通过对角距离图表示以一种新的方式呈现出来。
