Comparative structure analysis of proteinase inhibitors from the desert locust, Schistocerca gregaria
Comparative structure analysis of proteinase inhibitors from the desert locust, Schistocerca gregaria
复制标题
DOI：
10.1046/j.0014-2956.2001.02685.x
复制
发表时间：
2002-01-01
期刊：
影响因子：
--
通讯作者：
Perczel, A
中科院分区：
文献类型：
--
作者：
Gáspári, Z;Patthy, A;Perczel, A
用核磁共振方法测定了三种小分子丝氨酸蛋白酶抑制剂（两种天然蛋白和一种工程蛋白）SGCI（Schistocerca gregaria chymotrypsin inhibitor）、SGCI[L30 R，K31 M]和SGTI（Schistocerea gregaria trypsin inhibitor）的溶液结构。这些分子对靶蛋白酶表现出不同的特异性，其中SGCI是良好的胰凝乳蛋白酶抑制剂，其突变体是有效的胰蛋白酶抑制剂，而SGTI对这两种蛋白酶的抑制作用较弱。有趣的是，SGTI对昆虫蛋白酶的抑制作用比常规测定中使用的哺乳动物蛋白酶要好得多。所有三种分子都有一个类似的折叠，由三个反平行的β折叠片组成，有三个二硫桥。蛋白酶结合环在所有三种肽中具有稍微不同的几何形状。此外，结构的稳定性在SGCI和SGTI中是不同的。质子-氘交换实验表明，在SGTI中有一个高度刚性的核心，但在SGCI中没有。我们认为，所观察到的结构特性发挥了重要作用，这些抑制剂的特异性。
The solution structure of three small serine proteinase inhibitors, two natural and one engineered protein, SGCI (Schistocerca gregaria chymotrypsin inhibitor), SGCI[L30R, K31M] and SGTI (Schistocerea gregaria trypsin inhibitor), were determined by homonuclear NMR-spectroscopy. The molecules exhibit different specificities towards target proteinases, where SGCI is a good chymotrypsin inhibitor, its mutant is a potent trypsin inhibitor, and SGTI inhibits both proteinases weakly, Interestingly, SGTI is a much better inhibitor of insect proteinases than of the mammalian ones used in common assays. All three molecules have a similar fold composed from three antiparallel beta-pleated sheets with three disulfide bridges. The proteinase binding loop has a somewhat distinct geometry in all three peptides. Moreover, the stabilization of the structure is different in SGCI and SGTI. Proton-deuterium exchange experiments are indicative of a highly rigid core in SGTI but not in SGCI. We suggest that the observed structural properties play a significant role in the specificity of these inhibitors.