Streptokinase

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Streptokinase
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Chemical and physical data
FormulaC2100H3278N566O669S4
Molar mass47286.86 g·mol−1

Streptokinase is a

injection into a vein.[2]

Side effects include nausea, bleeding,

Streptokinase was discovered in 1933 from

beta-hemolytic streptococci.[5] It is on the World Health Organization's List of Essential Medicines.[6] It is no longer commercially available in the United States.[7]

Medical uses

If

tPA can be treated with aminocaproic acid
.

Contraindications

Absolute

  • Any prior intracranial hemorrhage
  • Known structural cerebral vascular lesion (e.g., arteriovenous malformation)
  • Known cancer inside the skull (primary or metastatic)
  • Ischemic stroke more than 4.5 hours and less than 3 months ago
  • Suspected aortic dissection
  • Active bleeding or bleeding problem other than menstruation
  • Significant closed-head or facial trauma within 3 months
  • Intracranial or intraspinal surgery within 2 months
  • Severe uncontrolled
    high blood pressure
    (unresponsive to emergency therapy)
  • For streptokinase, prior treatment within the previous 6 months

Relative

  • History of chronic, severe, poorly controlled hypertension
  • Significant hypertension on presentation (SBP >180 mm Hg or DBP >110 mm Hg)
  • History of prior ischemic stroke more than 3 month ago
  • Dementia
  • Known intracranial pathology not covered in absolute contraindications
  • Traumatic or prolonged (>10 min) CPR
  • Major surgery less than three weeks ago
  • Recent (within 2 to 4 wk) internal bleeding
  • Noncompressible vascular punctures
  • Active peptic ulcer
  • Oral anticoagulant therapy

[8]

Mechanism of action

Streptokinase C
Identifiers
OrganismStreptococcus dysgalactiae subsp. equisimilis
Symbolskc
UniProt
P00779
Search for
StructuresSwiss-model
DomainsInterPro
Staphylokinase/Streptokinase family
SCOP2
2sak / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDB1bml​, 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

substrate plasminogen 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 plasminogen. Deletion of Ile1 of streptokinase markedly inhibits its capacity to induce an active site in plasminogen, which supports the hypothesis that establishment of a salt bridge between Ile1 of streptokinase and Asp740 of plasminogen is necessary for streptokinase 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 streptokinase complex by 15 to 50 fold. These observations suggest that Lys698 is involved in formation of the initial streptokinase·plasminogen complex.[14]

Biology

Streptokinase is naturally produced by Streptococci spp. bacteria, which use this enzyme to break up blood clots so that they can spread from the initial site of infection. It can also activate fibrin.[15]

It is similar, both in function and in structure, to staphylokinase (Sak) found in Staphylococcus aureus. Staphylokinase is considered a virulence factor,[16] although its presence after the establishment of infection actually decreases disease severity. Both enzymes are carried by phages.[17]

History

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.[5]

Research

Streptokinase may find a use in helping to prevent

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.[18]
However, it has not been shown to be effective in humans in a clinical trial.

Marketing

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.

References

External links

  • "Streptokinase". Drug Information Portal. U.S. National Library of Medicine.