streptase

同

streptokinase

WordNet

1. an enzyme produced by some strains of streptococcus that can liquefy blood clots by converting plasminogen to plasmin; used medicinally in some cases of myocardial infarction and pulmonary embolism

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/01/03 03:17:58」(JST)

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Streptokinase C
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
Structure of staphylokinase, a plasminogen activator.
Identifiers
Symbol	Staphylokinase
Pfam	PF02821
InterPro	IPR004093
SCOP	2sak
SUPERFAMILY	2sak
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Streptokinase (SK) is a protein 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

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

Youtube Substrate Enzyme Mechanism Movie

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.

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

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	Unaffected	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

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.

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

English Journal

• In Vivo Anticoagulant and Thrombolytic Activities of a Fibrinolytic Serine Protease (Brevithrombolase) With the k-Carrageenan-Induced Rat Tail Thrombosis Model.

• Majumdar S1, Chattopadhyay P2, Mukherjee AK3.
• Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.Clin Appl Thromb Hemost.2016 Sep;22(6):594-8. doi: 10.1177/1076029615569567. Epub 2015 Feb 5.
• In the present study, in vivo thrombolysis efficiency of Brevithrombolase, a nontoxic fibrinolytic enzyme purified from Brevibacillus brevis strain FF02B, was affirmed by significant inhibition of thrombus formation in the k-carrageenan-induced rat tail, in a dose-dependent manner. Brevithrombolase
• PMID 25657326

• Streptococcus pyogenes Escapes Killing from Extracellular Histones through Plasminogen Binding and Activation by Streptokinase.

• Nitzsche R, Köhler J, Kreikemeyer B, Oehmcke-Hecht S.
• Journal of innate immunity.J Innate Immun.2016 Aug 18;8(6). [Epub ahead of print]
• Histones are small basic proteins and highly conserved among eukaryotes. Their main function is binding, packaging and organizing of DNA in the nucleus, but extracellular histones are also potent antimicrobial proteins. Here we found that Streptococcus pyogenes - an important human pathogen - protec
• PMID 27533300

• Infectious diseases and immunological responses in adult subjects with lifetime untreated, congenital GH deficiency.

• Campos VC1, Barrios MR2, Salvatori R3, de Almeida RP2, de Melo EV1, Nascimento AC1, de Jesus AR2, Aguiar-Oliveira MH1.
• Endocrine.Endocrine.2016 Aug 3. [Epub ahead of print]
• Growth hormone is important for the development and function of the immune system, but there is controversy on whether growth hormone deficiency is associated to immune disorders. A model of isolated growth hormone deficiency may clarify if the lack of growth hormone is associated with increased sus
• PMID 27484773

Japanese Journal

• Are the Various Thrombolytic Agents Equally Effective in the Treatment of Acute Transmural Myocardial Infarction?

• CLAESSENS Jan,HASELDONCKX Christiane
• Japanese Heart Journal 33(4), 413-421, 1992
• While it is no longer possible to imagine the treatment of an acute transmural myocardial infarction without the use of thrombolytic agents, some discussion still exists as to the choice of the thromb …
• NAID 130000765888

Related Links

• Streptase (Streptokinase): Side Effects, Interactions ...

Streptase®, Streptokinase, is a sterile, purified preparation of a bacterial protein elaborated by group C (beta) -hemolytic streptococci. It is supplied as a lyophilized white powder containing 25 mg cross-linked gelatin polypeptides, 25 ...

• Streptase Advanced Patient Information - Drugs.com

In the U.S. Streptase Available Dosage Forms: Powder for Solution Therapeutic Class: Thrombolytic Pharmacologic Class: Tissue Plasminogen Activator Uses For Streptase Streptokinase is used to dissolve blood clots that have ...

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リンク元	「ストレプトキナーゼ」

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英

streptokinase, SK

同

streptase

• 連鎖球菌(β型溶血性連鎖球菌)から放出されるタンパク質
• プラスミノゲン －(ストレプトキナーゼ)→　プラスミン
• 感染病巣の凝血塊を溶解し、感染拡大を促進するらしい。