t-PA K1区的同源模建及Kringle区与Lysine相互作用的研究

利用同源模建方法预测了ｔ－ＰＡＫ１区的三维结构。通过结构叠合确定了ｔ－ＰＡＫ１、Ｋ２区，纤溶酶原Ｋ１、Ｋ４区及ＵＫ Ｋ区的Ｌｙｓｉｎｅ结合口袋。静电势计算及疏水性分析表明，在ｔ－ＰＡ Ｋ２Ｃ Ａ２区以及纤溶酶原Ｋ１、Ｋ４区与纤维蛋白裸露的Ｌｙｓｉｎｅ之间在明显的的静电势互补和疏水面契合。确定了Ｋｒｉｎｇｌｅ区结合口袋与Ｌｙｓｉｎｅ亲和重要所基酸，分析了ｔ－ＰＡＫ１区，ＵＫ Ｋ区不能结合Ｌｙｓｉｎｅ

Homology Modeling of Tissue type Plasminogen Activator K1 Domain and Studies on the Interactions Between Kringles and Lysine

The 3 D structure of t PA K1 domain are predicted by the method of homology modeling.The putative lysine binding pockets of t PA K1,UK K,PLG K1 and K4 are determined by superposing their 3 D structures to that of t PA K2 domain,of which the lysine binding pockets have been revealed previously.After that the key residues of lysine binding pockets of kringles are identified.The structural analyses show that both of the electrostatic potential and hydrophobic complementarity are well matched between lysine and binding pockets of t PA K2,PLG K1 and K4,but for t PA K1 and UK K domains the complementarity do not matched well in one or both of the respects.It is proposed that this is the reason that t PA K1 and UK K domains do not bear the ability of binding lysine.With the respect of improving the affinity for fibrin,new type mutants of t PA K1 and UK K domain are designed,and structural changes caused by mutation are predicted by simulating the residue replacements.The mutant structural models demonstrate that the molecular design are reasonable.