Hatano K, Kojima M, Tanokura M, Takahashi K
Department of Biophysics and Biochemistry, Faculty of Science, University of Tokyo, Japan.
Biochemistry. 1996 Apr 30;35(17):5379-84. doi: 10.1021/bi952754+.
Bromelain inhibitor VI from pineapple stem (BI-VI) is a unique double-chain inhibitor with an 11-residue light chain and a 41-residue heavy chain by disulfide bonds and inhibits the cysteine proteinase bromelain competitively. The structure of BI-VI in aqueous solution was determined using nuclear magnetic resonance spectroscopy and simulated annealing-based calculations. Its three-dimensional structure was shown to be composed of two distinct domains, each of which is formed by a three-stranded antiparallel beta-sheet. Unexpectedly, BI-VI was found to share a similar folding and disulfide bond connectivities not with cystatin superfamily inhibitors which inhibit the same cysteine proteinases but with the Bowman-Birk trypsin/chymotrypsin inhibitor from soybean (BBI-I). BBI-I is a 71-residue inhibitor which has two independent inhibitory sites toward the serine proteinases trypsin and chymotrypsin. These structural similarities with BBI-I suggest that they have evolved from a common ancestor and differentiated in function during a course of molecular evolution.
菠萝茎中的菠萝蛋白酶抑制剂VI（BI-VI）是一种独特的双链抑制剂，通过二硫键连接一条11个残基的轻链和一条41个残基的重链，竞争性抑制半胱氨酸蛋白酶菠萝蛋白酶。利用核磁共振光谱和基于模拟退火的计算确定了BI-VI在水溶液中的结构。其三维结构显示由两个不同的结构域组成，每个结构域由三条反平行的β-折叠链形成。出乎意料的是，发现BI-VI与抑制相同半胱氨酸蛋白酶的胱抑素超家族抑制剂没有相似的折叠和二硫键连接方式，而是与大豆中的鲍曼-伯克胰蛋白酶/糜蛋白酶抑制剂（BBI-I）相似。BBI-I是一种71个残基的抑制剂，对丝氨酸蛋白酶胰蛋白酶和糜蛋白酶有两个独立的抑制位点。与BBI-I的这些结构相似性表明它们是从一个共同的祖先进化而来，并在分子进化过程中功能发生了分化。
