Summary: Staphylokinase/Streptokinase family
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Streptokinase Edit Wikipedia article
Complex of Catalytic Domain of Human Plasmin and Streptokinase; structure derived from PDB file 1BML.
|PDB||1BML (RCSB PDB PDBe PDBj)|
Structure of staphylokinase, a plasminogen activator.
Streptokinase (SK) is an enzyme secreted by several species of streptococci that can bind and activate human plasminogen. SK is used as an effective and inexpensive thrombolysis medication in some cases of myocardial infarction (heart attack) and pulmonary embolism. 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.
Mechanism of action
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. 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. 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. 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.
- Severe hypertension recent stroke
- Cerebral neoplasm
- Recent history of peptic ulcer disease
- Ulcerative colitis
- Subacute bacterial endocarditis
- Coagulation defects also due to liver or kidney disease
- Recent surgery
- Increased risk of cerebral bleeding
- Active internal bleeding
- Bleeding GI lesions.
Streptokinase is given intravenously as soon as possible after the onset of a heart attack to dissolve clots in the arteries of the heart wall. 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.
|Condition||Prothrombin time||Partial thromboplastin time||Bleeding time||Platelet count|
|Vitamin K deficiency or warfarin||Prolonged||Normal or mildly prolonged||Unaffected||Unaffected|
|Disseminated intravascular coagulation||Prolonged||Prolonged||Prolonged||Decreased|
|Von Willebrand disease||Unaffected||Prolonged or unaffected||Prolonged||Unaffected|
|Liver failure, early||Prolonged||Unaffected||Unaffected||Unaffected|
|Liver failure, end-stage||Prolonged||Prolonged||Prolonged||Decreased|
|Factor V deficiency||Prolonged||Prolonged||Unaffected||Unaffected|
|Factor X deficiency as seen in amyloid purpura||Prolonged||Prolonged||Unaffected||Unaffected|
|Bernard-Soulier syndrome||Unaffected||Unaffected||Prolonged||Decreased or unaffected|
|Factor XII deficiency||Unaffected||Prolonged||Unaffected||Unaffected|
Current research applications
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. However, it has not been shown to be effective in humans in a clinical trial.
Available in Viet Nam 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 Limited & Myokinase by Biocon Limited
- Rabijns A, De Bondt HL, De Ranter C (May 1997). "Three-dimensional structure of staphylokinase, a plasminogen activator with therapeutic potential". Nat. Struct. Biol. 4 (5): 357–60. doi:10.1038/nsb0597-357. PMID 9145104.
- Sikri N, Bardia A (2007). "A history of streptokinase use in acute myocardial infarction". Tex Heart Inst J 34 (3): 318–27. PMC 1995058. PMID 17948083.
- Meneveau N, Schiele F, Vuillemenot A, et al. (July 1997). "Streptokinase vs alteplase in massive pulmonary embolism. A randomized trial assessing right heart haemodynamics and pulmonary vascular obstruction". Eur. Heart J. 18 (7): 1141–8. PMID 9243149.
- Mundada L, Prorok, M (2003). "Structure-Function Analysis of Streptokinase Amino Terminus". Journal of Biological Chemistry 278 (3): 24421–24427. doi:10.1074/jbc.M301825200. PMID 5746739.
- Young, K Shi, G (1997). "Plasminogen Activation by Streptokinase iva a Unique Mechanism". Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital 34 (3): 1–13. PMID 5643782.[dead link]
- Loy, J, Lin,X (2001). "Domain Interactions between Streptokinase and Human Plasminogen". Biochemistry 48 (3): 14686–14695. doi:10.1021/bio11309d. PMID 45675.
- Wang, S, Reed, GL, Hedstrom, L (1999). "Deletion of Ile1 changes the mechanism of streptokinase: evidence for the molecular sexuality hypothesis". Biochemistry 38 (16): 5232–5240. doi:10.1021/bi981915h. PMID 10213631.
- Wang X, Lin X (1998). "Crystal Structure of Catalytic Domain of Human Plasmin Complexed with Streptokinase". Science Magazine 281 (3): 1662–1665. PMID 76543.
- A. Yagmurlu, M. Barlas, I. Gursel, I.H. Gokcora (2003). "Reduction of Surgery-Induced Peritoneal Adhesions by Continuous Release of Streptokinase from a Drug Delivery System". Eur Surg Res 35 (1): 46–49. doi:10.1159/000067035. PMID 12566787.
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Staphylokinase/Streptokinase family Provide feedback
No Pfam abstract.
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR004093Staphylokinases and streptokinases are not proteases. They are involved in plasminogen activation. The three-dimensional structure of streptokinase is believed to contain two independently folded domains, each homologous to serine proteases [PUBMED:6760891].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||serine-type endopeptidase activity (GO:0004252)|
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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|Author:||Bateman A, Griffiths-Jones SR|
|Number in seed:||11|
|Number in full:||458|
|Average length of the domain:||122.40 aa|
|Average identity of full alignment:||32 %|
|Average coverage of the sequence by the domain:||79.68 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||11|
|Download:||download the raw HMM for this family|
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This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
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Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
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The tree shows the occurrence of this domain across different species. More...
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For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
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We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
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There are 2 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Staphylokinase domain has been found. There are 31 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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