Streptokinase

Streptokinase is a thrombolytic medication

activating plasminogen by nonenzymatic
mechanism.[1] As a medication it is used
to break down clots in some cases of
myocardial infarction (heart attack),
pulmonary embolism, and arterial
thromboembolism.[2] The type of heart
attack it is used in is an ST elevation
myocardial infarction (STEMI).[3] It is given
by injection into a vein.[2]
 Streptokinase

Complex of catalytic domain of human

plasmin and streptokinase

Clinical data

Other names SK
AHFS/Drugs.com Micromedex Detailed
Consumer Information
(https://www.drugs.co
m/cons/streptokinase
-intravenous-intracoro
nary.html)
Routes of Intravenous
administration
ATC code B01AD01 (WHO (http
s://www.whocc.no/atc
_ddd_index/?code=B0
1AD01) )

Identifiers

CAS Number 9002-01-1 (https://co

mmonchemistry.cas.o
rg/detail?cas_rn=9002
-01-1)
DrugBank DB00086 (https://ww
w.drugbank.ca/drugs/
DB00086)
ChemSpider none
UNII 8X1OXL3SNU (http
s://precision.fda.gov/
 uniisearch/srs/unii/8X
1OXL3SNU)
ECHA InfoCard 100.029.667 (https://e
cha.europa.eu/substa
nce-information/-/sub
stanceinfo/100.029.6
67)

Chemical and physical data

Formula C2100H3278N566O669S4
Molar mass 47 286.86 g·mol−1

Side effects include nausea, bleeding, low

blood pressure, and allergic reactions.[2] A
second use in a person's lifetime is not
recommended.[2] While no harm has been
found with use in pregnancy, it has not
been well studied in this group.[4]
Streptokinase is in the antithrombotic
family of medications and works by
turning on the fibrinolytic system.[3]

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 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.

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

Organism Streptococcus
dysgalactiae subsp.
equisimilis (https://ww
w.ncbi.nlm.nih.gov/Ta
xonomy/Browser/ww
wtax.cgi?name=Strept
ococcus+dysgalactiae
+subsp.+equisimilis&r
n=1)

Symbol skc

Entrez 8110746 (https://ww

w.ncbi.nlm.nih.gov/ge
 ne?cmd=retrieve&dopt
=default&rn=1&list_ui
ds=8110746)

PDB 1BML (https://www.rc

sb.org/structure/1BM
L)

UniProt P00779 (https://www.

uniprot.org/uniprot/P0
0779)
 Search for

Structures Swiss-model (https://s

wissmodel.expasy.org/r
epository/uniprot/P007
79)

Domains InterPro (https://www.e

bi.ac.uk/interpro/protei
n/P00779)
 Staphylokinase/Streptokinase family

Structure of staphylokinase, a plasminogen

activator.[9]

Identifiers

Symbol Staphylokinase

Pfam PF02821 (https://ww

w.ebi.ac.uk/interpro/e
ntry/pfam/PF02821)

InterPro IPR004093 (https://w

ww.ebi.ac.uk/interpro/
entry/IPR004093)
SCOP2 2sak (http://scop2.mr
c-lmb.cam.ac.uk/sear
ch?t=txt;q=2sak) /
SCOPe (https://scop.b
erkeley.edu/pdb/code
=2sak) / SUPFAM (ht
tp://supfam.org/SUPE
RFAMILY/cgi-bin/sear
ch.cgi?search_field=2
sak)
 Available protein structures:

Pfam structures (http://pfam.

xfam.org/family/PF028
21?tab=pdbBlock) /
ECOD (http://prodata.s
wmed.edu/ecod/compl
ete/search?kw=PF0282
1)  

PDB RCSB PDB (https://ww

w.rcsb.org/search?q=rc
sb_polymer_entity_ann
otation.annotation_id:P
F02821%20AND%20rcs
b_polymer_entity_anno
tation.type:Pfam) ;
PDBe (https://www.ebi.
ac.uk/pdbe/entry/searc
h/index?pfam_accessio
 n:PF02821) ; PDBj (http
s://pdbj.org/searchFor?
query=PF02821)

PDBsum structure summary (htt

ps://www.ebi.ac.uk/thor
nton-srv/databases/cgi
-bin/pdbsum/GetPfamS
tr.pl?pfam_id=PF0282
1)

PDB 1bml (https://www.rcs

b.org/structure/1bml) ​,
1bui (https://www.rcsb.
org/structure/1bui) ​,
1c4p (https://www.rcsb.
org/structure/1c4p) ​,
1c76 (https://www.rcsb.
org/structure/1c76) ​,
1c77 (https://www.rcsb.
org/structure/1c77) ​,
1c78 (https://www.rcsb.
org/structure/1c78) ​,
1c79 (https://www.rcsb.
org/structure/1c79) ​,
1l4d (https://www.rcsb.
org/structure/1l4d) ​,
1l4z (https://www.rcsb.
org/structure/1l4z) ​,
1qqr (https://www.rcsb.
org/structure/1qqr) ​,
1ssn (https://www.rcsb.
org/structure/1ssn) ​,
2sak (https://www.rcsb.
org/structure/2sak) ​
Proposed counterion for Asp740 is Lys698 create salt-bridge

S ubstrate 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 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. When
streptokinase is present, it binds to
plasminogen to form a complex
(streptokinase·plasminogen) that converts
substrate plasminogen to plasmin.
Residues 1–59 of streptokinase regulate
its capacity to induce an active site in
bound plasminogen by a nonproteolytic
mechanism and to activate 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.[18]

Research
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.

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
1. Mican, Jan; Toul, Martin; Bednar, David;
Damborsky, Jiri (2019). "Structural Biology
and Protein Engineering of Thrombolytics"
(https://doi.org/10.1016%2Fj.csbj.2019.06.
023) . Computational and Structural
Biotechnology Journal. 17: 917–938.
doi:10.1016/j.csbj.2019.06.023 (https://do
i.org/10.1016%2Fj.csbj.2019.06.023) .
PMC 6637190 (https://www.ncbi.nlm.nih.g
ov/pmc/articles/PMC6637190) .
PMID 31360331 (https://pubmed.ncbi.nlm.
nih.gov/31360331) .
2. World Health Organization (2009). Stuart
MC, Kouimtzi M, Hill SR (eds.). WHO Model
Formulary 2008. World Health
Organization. pp. 291–2. hdl:10665/44053
(https://hdl.handle.net/10665%2F44053) .
ISBN 9789241547659.

3. "Streptokinase 1,500,000 iu - Summary of

Product Characteristics (SPC) - (eMC)" (http
s://www.medicines.org.uk/emc/medicine/2
6905) . www.medicines.org.uk. 1 July
2015. Archived (https://web.archive.org/we
b/20161220184417/https://www.medicine
s.org.uk/emc/medicine/26905) from the
original on 20 December 2016. Retrieved
14 December 2016.
4. "Streptokinase Use During Pregnancy |
Drugs.com" (https://www.drugs.com/pregn
ancy/streptokinase.html) .
www.drugs.com. Archived (https://web.arc
hive.org/web/20161221010155/https://ww
w.drugs.com/pregnancy/streptokinase.htm
l) from the original on 21 December 2016.
Retrieved 14 December 2016.

5. Sikri N, Bardia A (2007). "A history of

streptokinase use in acute myocardial
infarction" (https://www.ncbi.nlm.nih.gov/p
mc/articles/PMC1995058) . Texas Heart
Institute Journal. 34 (3): 318–27.
PMC 1995058 (https://www.ncbi.nlm.nih.g
ov/pmc/articles/PMC1995058) .
PMID 17948083 (https://pubmed.ncbi.nlm.
nih.gov/17948083) .
6. World Health Organization (2019). World
Health Organization model list of essential
medicines: 21st list 2019. Geneva: World
Health Organization. hdl:10665/325771 (htt
ps://hdl.handle.net/10665%2F325771) .
WHO/MVP/EMP/IAU/2019.06. License: CC
BY-NC-SA 3.0 IGO.

7. "streptokinase (Intravenous route,

Intracoronary route)" (https://www.drugs.co
m/cons/streptokinase-intravenous-intracor
onary.html) . Truven Health Analytics.
Archived (https://web.archive.org/web/201
51208092537/http://www.drugs.com/con
s/streptokinase-intravenous-intracoronary.h
tml) from the original on 8 December
2015. Retrieved 28 November 2015.
8. O'Gara PT, Kushner FG, Ascheim DD, Casey
DE, Chung MK, de Lemos JA, et al. (January
2013). "2013 ACCF/AHA guideline for the
management of ST-elevation myocardial
infarction: a report of the American College
of Cardiology Foundation/American Heart
Association Task Force on Practice
Guidelines" (https://doi.org/10.1161%2FCI
R.0b013e3182742cf6) . Circulation. 127
(4): e362-425.
doi:10.1161/CIR.0b013e3182742cf6 (http
s://doi.org/10.1161%2FCIR.0b013e318274
2cf6) . PMID 23247304 (https://pubmed.nc
bi.nlm.nih.gov/23247304) .
9. Rabijns A, De Bondt HL, De Ranter C (May
1997). "Three-dimensional structure of
staphylokinase, a plasminogen activator
with therapeutic potential". Nature
Structural Biology. 4 (5): 357–60.
doi:10.1038/nsb0597-357 (https://doi.org/
10.1038%2Fnsb0597-357) . PMID 9145104
(https://pubmed.ncbi.nlm.nih.gov/914510
4) . S2CID 32914387 (https://api.semantic
scholar.org/CorpusID:32914387) .
10. Mundada LV, Prorok M, DeFord ME, Figuera
M, Castellino FJ, Fay WP (July 2003).
"Structure-function analysis of the
streptokinase amino terminus (residues 1-
59)" (https://doi.org/10.1074%2Fjbc.M301
825200) . The Journal of Biological
Chemistry. 278 (27): 24421–7.
doi:10.1074/jbc.M301825200 (https://doi.o
rg/10.1074%2Fjbc.M301825200) .
PMID 12704199 (https://pubmed.ncbi.nlm.
nih.gov/12704199) .
11. Young KC, Shi GY, Wu DH, Chang LC, Chang
BI, Ou CP, Wu HL (January 1998).
"Plasminogen activation by streptokinase
via a unique mechanism" (https://doi.org/1
0.1074%2Fjbc.273.5.3110) . The Journal of
Biological Chemistry. 273 (5): 3110–6.
doi:10.1074/jbc.273.5.3110 (https://doi.or
g/10.1074%2Fjbc.273.5.3110) .
PMID 9446629 (https://pubmed.ncbi.nlm.ni
h.gov/9446629) .
12. Loy JA, Lin X, Schenone M, Castellino FJ,
Zhang XC, Tang J (December 2001).
"Domain interactions between
streptokinase and human plasminogen".
Biochemistry. 40 (48): 14686–95.
doi:10.1021/bi011309d (https://doi.org/10.
1021%2Fbi011309d) . PMID 11724583 (htt
ps://pubmed.ncbi.nlm.nih.gov/11724583) .

13. Wang S, Reed GL, Hedstrom L (April 1999).

"Deletion of Ile1 changes the mechanism of
streptokinase: evidence for the molecular
sexuality hypothesis". Biochemistry. 38
(16): 5232–40. doi:10.1021/bi981915h (htt
ps://doi.org/10.1021%2Fbi981915h) .
PMID 10213631 (https://pubmed.ncbi.nlm.
nih.gov/10213631) .
14. Wang X, Lin X, Loy JA, Tang J, Zhang XC
(September 1998). "Crystal structure of the
catalytic domain of human plasmin
complexed with streptokinase". Science.
281 (5383): 1662–5.
doi:10.1126/science.281.5383.1662 (http
s://doi.org/10.1126%2Fscience.281.5383.1
662) . PMID 9733510 (https://pubmed.ncb
i.nlm.nih.gov/9733510) .
15. Wang H, Lottenberg R, Boyle MD (March
1995). "Analysis of the interaction of group
A streptococci with fibrinogen,
streptokinase and plasminogen". Microbial
Pathogenesis. 18 (3): 153–66.
doi:10.1016/S0882-4010(95)90013-6 (http
s://doi.org/10.1016%2FS0882-4010%289
5%2990013-6) . PMID 7565010 (https://pu
bmed.ncbi.nlm.nih.gov/7565010) .

16. Bokarewa MI, Jin T, Tarkowski A (2006).

"Staphylococcus aureus: Staphylokinase".
The International Journal of Biochemistry &
Cell Biology. 38 (4): 504–9.
doi:10.1016/j.biocel.2005.07.005 (https://d
oi.org/10.1016%2Fj.biocel.2005.07.005) .
PMID 16111912 (https://pubmed.ncbi.nlm.
nih.gov/16111912) .
17. Kwiecinski J, Jacobsson G, Karlsson M, Zhu
X, Wang W, Bremell T, Josefsson E, Jin T
(September 2013). "Staphylokinase
promotes the establishment of
Staphylococcus aureus skin infections
while decreasing disease severity" (https://
doi.org/10.1093%2Finfdis%2Fjit288) . The
Journal of Infectious Diseases. 208 (6):
990–9. doi:10.1093/infdis/jit288 (https://d
oi.org/10.1093%2Finfdis%2Fjit288) .
PMID 23801604 (https://pubmed.ncbi.nlm.
nih.gov/23801604) .
18. Sikri N, Bardia A (2007). "A history of
streptokinase use in acute myocardial
infarction" (https://www.ncbi.nlm.nih.gov/p
mc/articles/PMC1995058) . Texas Heart
Institute Journal. 34 (3): 318–27.
PMC 1995058 (https://www.ncbi.nlm.nih.g
ov/pmc/articles/PMC1995058) .
PMID 17948083 (https://pubmed.ncbi.nlm.
nih.gov/17948083) .
19. Yagmurlu A, Barlas M, Gursel I, Gokcora IH
(2003). "Reduction of surgery-induced
peritoneal adhesions by continuous release
of streptokinase from a drug delivery
system". European Surgical Research. 35
(1): 46–9. doi:10.1159/000067035 (https://
doi.org/10.1159%2F000067035) .
PMID 12566787 (https://pubmed.ncbi.nlm.
nih.gov/12566787) . S2CID 37453555 (http
s://api.semanticscholar.org/CorpusID:3745
3555) .

External links
"Streptokinase" (https://druginfo.nlm.nih.
gov/drugportal/name/streptokinase) .
Drug Information Portal. U.S. National
Library of Medicine.
 Portal: Medicine

Retrieved from
"https://en.wikipedia.org/w/index.php?
title=Streptokinase&oldid=1145254702"

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