Hijikata-Okunomiya A, Okamoto S, Kikumoto R, Tamao Y, Ohkubo K, Tezuka T, Tonomura S, Matsumoto O
Thromb Res. 1987 Mar 1;45(5):451-62. doi: 10.1016/0049-3848(87)90308-2.
The relationship between chemical modifications of arginine derivatives and inhibitory activity to trypsin, plasmin and glandular kallikrein was investigated comparing with that of thrombin and concluded as follows: The hydrophobic binding pocket, which has been reported previously to be stereogeometrically very similar in trypsin and thrombin, corresponded to the length of ethylpiperidine. Concerning the site (termed the P site) next to the hydrophobic binding pocket, there were large differences in stereogeometry between trypsin and thrombin; the binding site of trypsin extended further to allow propyl and phenyl group attached to piperidine, while that of thrombin would be much narrower and unable to allow them. The P sites of plasmin and glandular kallikrein resembled that of trypsin in being able to allow phenyl group. To substantialize the hydrophobic binding pocket and the P site, a (2R, 4R)-MQPA-trypsin complex model was generated using the results of X-ray crystallography of (2R, 4R)-MQPA and BPTI-trypsin complex by calculation to minimize van der Waals contacts, and it was of great use for understanding the geometry of the active sites of trypsin, thrombin, plasmin and glandular kallikrein.
研究了精氨酸衍生物的化学修饰与对胰蛋白酶、纤溶酶和腺体激肽释放酶的抑制活性之间的关系，并与凝血酶进行了比较，结果如下：先前报道在胰蛋白酶和凝血酶中立体几何结构非常相似的疏水结合口袋，与乙基哌啶的长度相对应。关于疏水结合口袋旁边的位点（称为P位点），胰蛋白酶和凝血酶在立体几何结构上存在很大差异；胰蛋白酶的结合位点延伸得更远，以允许哌啶连接丙基和苯基，而凝血酶的结合位点则要窄得多，无法容纳它们。纤溶酶和腺体激肽释放酶的P位点在能够容纳苯基方面与胰蛋白酶相似。为了使疏水结合口袋和P位点实体化，利用(2R, 4R)-MQPA与BPTI-胰蛋白酶复合物的X射线晶体学结果，通过计算生成了(2R, 4R)-MQPA-胰蛋白酶复合物模型，以最小化范德华接触，这对于理解胰蛋白酶、凝血酶、纤溶酶和腺体激肽释放酶活性位点的几何结构非常有用。
