Ginalski K, Lesyng B, Sowadski J, Wojciechowski M
Interdisciplinary Centre for Mathematical and Computational Modelling, Department of Biophysics, Warsaw University, Poland.
Acta Biochim Pol. 1997;44(3):557-64.
An active form of p38 protein kinase, belonging to the mitogen-activated protein kinases subfamily, has been designed based on crystallographically known structures of two other kinases, an active form of protein kinase A (PKA) and an inactive form of extracellular signal-regulated kinase 2 (ERK2). The modelling procedure is described. Its general scheme can also be applied to other kinases. The structure of the active forms of p38 and PKA is very similar in the region which binds the substrate. The ATP-binding mode is very similar in the active forms of all the three studied kinases. Models of the active forms allow for further studies on transphosphorylation processes at the molecular level, and modelling of inhibitors competitive with ATP and/or substrates.
p38蛋白激酶的一种活性形式属于丝裂原活化蛋白激酶亚家族，它是基于另外两种激酶的晶体学已知结构设计而成的，这两种激酶分别是蛋白激酶A（PKA）的活性形式和细胞外信号调节激酶2（ERK2）的非活性形式。文中描述了建模过程。其总体方案也可应用于其他激酶。p38和PKA活性形式的结构在结合底物的区域非常相似。在所研究的三种激酶的活性形式中，ATP结合模式非常相似。活性形式的模型有助于在分子水平上进一步研究转磷酸化过程，以及对与ATP和/或底物竞争的抑制剂进行建模。
