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 was predicted by the method of homology modeling. The putative lysine-binding pockets of t-PA K1, UK K, PLG K1 and K4 were determined by superimposing their 3-D structures to that of t-PA K2 domain, of which the lysine-binding pockets had been revealed previously. After that the key residues of lysine-binding pockets of kringles were identified. The structural analyses showed that both the electrostatic potential and hydrophobic complementarity were well matched between lysine and the binding pockets of t-PA K2, PLG K1 and K4, but for t-PA K1 and UK K domains the complementarity did not match well in one or both respects. It is proposed that this is the reason that t-PA K1 and UK K domains do not bear the ability to bind lysine. With the respect of improving the affinity for fibrin, new types of mutants of t-PA K1 and UK K domains were designed, and structural changes caused by mutation were predicted by simulating the residue replacements. The mutant structural models demonstrated that the molecular design was reasonable.
Wang
G
G
Beijing Institute of Biotechnology, China.
Liu
S
S
Xu
X
X
Huang
P
P
Huang
C
C
D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D018082:Kringles; D008239:Lysine / Q000737:chemistry; D008958:Models, Molecular; D010446:Peptide Fragments; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D010959:Tissue Plasminogen Activator / Q000737:chemistry*
D010446:Peptide Fragments; D010959:Tissue Plasminogen Activator; D008239:Lysine