Streptokinase

If percutaneous coronary intervention (PCI) is not available within 90–120 minutes of first contact, streptokinase is recommended intravenously as soon as possible after the onset of a ST elevation myocardial infarction (STEMI). As streptokinase is a bacterial product, the body has the ability to build up an immunity to it. Therefore, it is recommended that this medication should not be used again after four days from the first administration, as it may not be as effective and can also cause an allergic reaction. For this reason, it is usually given only for a person's first heart attack. Further thrombotic events could be treated with tissue plasminogen activator (tPA). Overdose of streptokinase or tPA can be treated with aminocaproic acid.

Staphylokinase/Streptokinase family
Structure of staphylokinase, a plasminogen activator.[9]
Identifiers
Symbol	Staphylokinase
Pfam	PF02821
InterPro	IPR004093
SCOPe	2sak / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary PDB 1bml​, 1bui​, 1c4p​, 1c76​, 1c77​, 1c78​, 1c79​, 1l4d​, 1l4z​, 1qqr​, 1ssn​, 2sak​

Proposed counterion for Asp740 is Lys698 create salt-bridge

Substrate Enzyme Mechanism Movie

Streptokinase belongs to a group of medications known as fibrinolytics, and complexes of streptokinase with human plasminogen can hydrolytically activate other unbound plasminogen by activating through bond cleavage to produce plasmin. There are three domains to streptokinase, denoted α (residues 1–150), β (residues 151–287), and γ (residues 288–414). Each domain binds plasminogen, although none can activate plasminogen independently.[10]

Plasmin is produced in the blood to break down fibrin, the major constituent of blood thrombi, thereby dissolving clots once they have fulfilled their purpose of stopping bleeding. Extra production of plasmin caused by streptokinase breaks down unwanted blood clots, for example, in the lungs (pulmonary embolism). The usual activation of plasminogen (Plgn) is by proteolysis of the Arg561—Val562 bond.[11] The amino group of Val562 then forms a salt-bridge with Asp740, which triggers a conformational change producing the active protease Plasmin (Pm). When (SK) is present, it binds to Plgn to form a complex (SK. Plgn) that converts substrate Plgn to Pm. Residues 1–59 of SK regulate its capacity to induce an active site in bound Pg by a nonproteolytic mechanism and to activate substrate Pg in a fibrin-independent manner. This complex subsequently rearranges to an active complex although the Arg561–Val562 bond remains intact. Therefore, another residue must substitute for the free amino group of Val562 and provide a counterion for Asp740 in this active complex.[12] Two candidates for this counterion have been suggested: Ile1 of streptokinase and Lys698 of Plgn. Deletion of Ile1 of SK markedly inhibits its capacity to induce an active site in plasminogen, which supports the hypothesis that establishment of a salt bridge between Ile1 of SK and Asp740 of plasminogen is necessary for SK to induce an active site in plasminogen by a nonproteolytic mechanism.[13] In contrast with the Ile1 substitutions, the Lys698 mutations also decreased the dissociation constant of the SK complex by 15 to 50 fold. These observations suggest that Lys698 is involved in formation of the initial SK·Plgn complex.[14]

After many years of work along with his student Sol Sherry, William S. Tillett discovered streptokinase in 1933. Initially used in treatment of fibrinous pleural exudates, hemothorax and tuberculous meningitis, its role in acute myocardial infarction was serendipitous.[18]

Streptokinase may find a use in helping to prevent postoperative adhesions, a common complication of surgery, especially abdominal surgery (appendectomy, gall stones, hysterectomy, etc.) One study using animal models (rats) found that when used with a PHBV membrane drug-delivery system, it was 90 percent effective in preventing adhesions.[19] However, it has not been shown to be effective in humans in a clinical trial.

It is marketed in Chile as Streptase by Alpes Selection, under license of CSL Behring Germany.

Available in Vietnam under the name Mutose. Available in Cuba, Venezuela, Ecuador and other Latin American countries under the trademark Heberkinasa, commercialized by Heber Biotech, Havana, Cuba. Available in India under the name STPase by Cadila Pharmaceuticals, and Myokinase by Biocon Limited.