Abstract: Similar to other serine proteinases, the pertinent active site amino acids are preserved in urokinase and the amino acids forming the specific pocket shows a considerable homology with other serine proteinases, especially with trypsin. But urokinase can not be inhibited by pancreatic trypsin inhibitor (PTI) which is the best inhibitor of trypsin. Using Chou-Fasman and ECEPP/2 programs the secondary structure and tertiary structure of urokinase fragments 177-189(UKf2)and 245-255 (UKf1) were predicted in order to investigate the reason of different activities between urokinase and trypsin.
The results showed that amino acids 246-252 in UKf1 formed a α-helix structure. The dihedral angles φ of these residues were around -57° and Ψ -47°. Amino acids 185-188 in UKf2 formd a β-sheet, 181-184 were in a β-turn structure. Comparing with the stereoscopric structure of the corresponding fragments in trypsin, it can be found that since the lack of two residues in trypsin in the fragment corresponding to UKf1, only a turn structure existed in this fragment. The existance of α-helix structure in UKf1 hindered the combining of PT1 with the active sites of UK and made urokinase not being inhibited by PTI.