Homology Modeling of Tissue type Plasminogen Activator K1 Domain and Studies on the Interactions Between Kringles and Lysine
t-PA K1区的同源模建及Kringle区与Lysine相互作用的研究

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.