Interaction of streptokinase and plasminogen. Studied with truncated streptokinase peptides.
The interaction of streptokinase (SK) with human plasminogen (HPlg) was investigated using truncated SK peptides prepared by gene cloning techniques. SK(16-414) and SK(16-378) could activate HPlg as efficiently as the authentic SK. SK(60-414), which had been preincubated with SK(1-59), could also activate HPlg. SK(91-414), SK(127-414), and SK(158-414), at a concentration of one-tenth of HPlg, all failed to activate HPlg. However, the truncated SK peptides in complexes with equimolar HPlg could form amidolytically active virgin enzymes that slowly converted to human plasmin (HPlm) after a lag period of 15 min. SK(16-316) could not activate HPlg. No virgin enzyme was detected when SK(16-316) was incubated with equimolar HPlg, but the HPlg in the complex was modified to HPlm after reaction for 20 min. SK(220-414) and SK(16-251) had no ability to transform HPlg to virgin enzyme or to HPlm in equimolar complex with HPlg, although they could bind to HPlg. The functions of five regions in the SK molecule (a, Ile1-Lys59; b, Ser60-Asn90; c, Val158-Arg219; d, Tyr252-Ala316; e, Ser317-Ala378) in interaction with HPlg are deduced. Region a is important in stabilizing the conformation of the SK molecule, and region b is essential for HPlg activation. Region c is required for induction of the conformational changes of HPlg to virgin enzyme. Regions c and d are required for the conversion of HPlg to HPlm in the HPlg.SK equimolar complex. Coordination of regions c, d, and e of SK is essential for a virgin enzyme formation, and coordination of regions b, c, d and e is required for an effective SK-type HPlg activator.
D001483:Base Sequence; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D010958:Plasminogen / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013300:Streptokinase / Q000737:chemistry*; D013329:Structure-Activity Relationship
D010446:Peptide Fragments; D010958:Plasminogen; D013300:Streptokinase