Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
31  structures 171  species 2  interactions 458  sequences 3  architectures

Family: Staphylokinase (PF02821)

Summary: Staphylokinase/Streptokinase family

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Streptokinase". More...

Streptokinase Edit Wikipedia article

Streptokinase C
Sk surface 3.png
Complex of Catalytic Domain of Human Plasmin and Streptokinase; structure derived from PDB file 1BML.
Identifiers
Symbol skc
Entrez 8110746
PDB 1BML (RCSB PDB PDBe PDBj)
UniProt P00779
Other data
Staphylokinase/Streptokinase family
PDB 2sak EBI.jpg
Structure of staphylokinase, a plasminogen activator.[1]
Identifiers
Symbol Staphylokinase
Pfam PF02821
InterPro IPR004093
SCOP 2sak
SUPERFAMILY 2sak

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)[2] and pulmonary embolism.[3] 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.[4]

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[5]

Contraindications

  • Severe hypertension recent stroke
  • Cerebral neoplasm
  • Recent history of peptic ulcer disease
  • Ulcerative colitis
  • Pancreatitis
  • Subacute bacterial endocarditis
  • Coagulation defects also due to liver or kidney disease
  • Recent surgery
  • Childbirth.
  • Hypersensitivity
  • Increased risk of cerebral bleeding
  • Trauma
  • Pregnancy
  • Active internal bleeding
  • Bleeding GI lesions.

Administration

If PCI is not available within 90 minutes of first contact, 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.

Laboratory findings in various platelet and coagulation disorders (V - T)
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
Hemophilia Unaffected Prolonged Prolonged Unaffected
Aspirin Unaffected Unaffected Prolonged Unaffected
Thrombocytopenia Unaffected Unaffected Prolonged Decreased
Liver failure, early Prolonged Unaffected Unaffected Unaffected
Liver failure, end-stage Prolonged Prolonged Prolonged Decreased
Uremia Unaffected Unaffected Prolonged Unaffected
Congenital afibrinogenemia Prolonged Prolonged Prolonged Unaffected
Factor V deficiency Prolonged Prolonged Unaffected Unaffected
Factor X deficiency as seen in amyloid purpura Prolonged Prolonged Unaffected Unaffected
Glanzmann's thrombasthenia Unaffected Unaffected Prolonged Unaffected
Bernard-Soulier syndrome Unaffected Unaffected Prolonged Decreased or unaffected
Factor XII deficiency Unaffected Prolonged Unaffected Unaffected
C1INH deficiency Unaffected Shortened Unaffected Unaffected

Mechanism of action

Proposed counterion for Asp740 is Lys698 create salt-bridge; structure derived from PDB file 1BML

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.[6] 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.[7] 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.[8] 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.[9]

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.[10] 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 ZLB Behring from Marburg, Germany.

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

References

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. doi:10.1093/oxfordjournals.eurheartj.a015410. PMID 9243149. 
  4. ^ 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. 
  5. ^ "WHO Model List of EssentialMedicines". World Health Organization. October 2013. Retrieved 22 April 2014. 
  6. ^ 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]
  7. ^ Loy, J, Lin,X (2001). "Domain Interactions between Streptokinase and Human Plasminogen". Biochemistry 48 (3): 14686–14695. doi:10.1021/bio11309d. PMID 45675. 
  8. ^ 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. 
  9. ^ Wang X, Lin X (1998). "Crystal Structure of Catalytic Domain of Human Plasmin Complexed with Streptokinase". Science Magazine 281 (3): 1662–1665. doi:10.1126/science.281.5383.1662. PMID 76543. 
  10. ^ 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. 

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Staphylokinase/Streptokinase family Provide feedback

No Pfam abstract.

Literature references

  1. Rabijns A, De Bondt HL, De Ranter C; , Nat Struct Biol 1997;4:357-360.: Three-dimensional structure of staphylokinase, a plasminogen activator with therapeutic potential. PUBMED:9145104 EPMC:9145104


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR004093

Staphylokinases 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].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(11)
Full
(458)
Representative proteomes NCBI
(340)
Meta
(0)
RP15
(1)
RP35
(4)
RP55
(7)
RP75
(11)
Jalview View  View  View  View  View  View  View   
HTML View  View  View  View  View  View     
PP/heatmap 1 View  View  View  View  View     
Pfam viewer View  View             

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(11)
Full
(458)
Representative proteomes NCBI
(340)
Meta
(0)
RP15
(1)
RP35
(4)
RP55
(7)
RP75
(11)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(11)
Full
(458)
Representative proteomes NCBI
(340)
Meta
(0)
RP15
(1)
RP35
(4)
RP55
(7)
RP75
(11)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: PDB
Previous IDs: none
Type: Domain
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 information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.7 21.7
Trusted cut-off 21.9 31.2
Noise cut-off 21.5 21.1
Model length: 125
Family (HMM) version: 11
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Show

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Interactions

There are 2 interactions for this family. More...

Trypsin Staphylokinase

Structures

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.

Loading structure mapping...