Characterization of a novel streptokinase produced by Streptococcus equisimilis of non-human origin.
Abstract: Streptokinases are proteins with plasminogen activator activity produced by certain hemolytic streptococci. We previously identified equine streptococcal isolates which produced streptokinases (ESKs) that bound both human and equine plasminogen but only readily activated equine plasminogen (14). This property was exploited to purify a representative ESK produced by Streptococcus equisimilis strain 87-542-W. Affinity chromatography with human plasminogen resulted in the isolation of a M(r) approximately 49,000 molecule with two isoforms. This ESK was subsequently compared to well characterized streptokinases (HSKs) that efficiently activate human plasminogen. Differences in streptokinases were identified in the highly conserved amino-terminal amino acid sequence, peptide maps, and antigenic properties, and these differences were supported by DNA hybridization studies. These results indicate that the family of proteins identified as streptokinases has much greater diversity than previously appreciated.
Publication Date: 1994-10-01 PubMed ID: 7878639
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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This study investigates a novel form of the protein streptokinase, produced by Streptococcus equisimilis from horses, discovering it possesses unique properties and greater diversity than the previously understood forms of this protein.
Introduction
- The research revolves around streptokinases, which are proteins produced by certain forms of hemolytic streptococci, a type of bacteria. These proteins have the capacity to activate plasminogen, a precursor to the enzyme plasmin, involved in the breaking down of blood clots.
Methodology
- The researchers studied isolates from horse streptococci which produced streptokinases, named in this context Equine Streptokinases (ESKs). These ESKs showed the ability to bind both human and equine (horse) plasminogen but predominantly activated equine plasminogen.
- This distinction was used to purify a representative ESK through a process known as affinity chromatography with human plasminogen.
- The purification led to an isolated molecule, designated ‘M(r) approximately 49,000’, with two isoforms, that denotes the molecular weight of the molecule.
Comparison with Other Streptokinases
- This isolated ESK was then compared to other well-studied streptokinases, identified as Human Streptokinases (HSKs), which are known to efficiently activate human plasminogen.
- Differences between the ESK and the HSKs were identified in several areas including the highly conserved amino-terminal amino acid sequence, antigenic properties, and peptide maps, which are all used in identifying and classifying proteins.
- These differences were supported further by DNA hybridization studies which is a molecular biology method to study the presence and measuring the amount of specific DNA or RNA molecules in cells or tissues.
Conclusion
- The findings from the research indicate a much greater diversity in the family of proteins termed as streptokinases than previously understood or reported. This suggests more room for future study and potential application in the medical and biological fields.
Cite This Article
APA
Nowicki ST, Minning-Wenz D, Johnston KH, Lottenberg R.
(1994).
Characterization of a novel streptokinase produced by Streptococcus equisimilis of non-human origin.
Thromb Haemost, 72(4), 595-603.
Publication
Researcher Affiliations
- Department of Medicine, College of Medicine, University of Florida, Gainesville.
MeSH Terms
- Amino Acid Sequence
- Animals
- Antibodies, Bacterial / immunology
- Chromatography, Affinity
- Consensus Sequence
- DNA, Bacterial / genetics
- Enzyme Activation
- Horses / microbiology
- Isoelectric Focusing
- Molecular Sequence Data
- Peptide Mapping
- Plasminogen / metabolism
- Protein Binding
- Sequence Alignment
- Sequence Homology, Amino Acid
- Species Specificity
- Streptococcus / enzymology
- Streptococcus / isolation & purification
- Streptokinase / classification
- Streptokinase / genetics
- Streptokinase / immunology
- Streptokinase / isolation & purification
Grant Funding
- HL 07489 / NHLBI NIH HHS
- HL 41898 / NHLBI NIH HHS
Citations
This article has been cited 6 times.- Sun H, Xu Y, Sitkiewicz I, Ma Y, Wang X, Yestrepsky BD, Huang Y, Lapadatescu MC, Larsen MJ, Larsen SD, Musser JM, Ginsburg D. Inhibitor of streptokinase gene expression improves survival after group A streptococcus infection in mice. Proc Natl Acad Sci U S A 2012 Feb 28;109(9):3469-74.
- Sun H, Wang X, Degen JL, Ginsburg D. Reduced thrombin generation increases host susceptibility to group A streptococcal infection. Blood 2009 Feb 5;113(6):1358-64.
- Ward PN, Leigh JA. Characterization of PauB, a novel broad-spectrum plasminogen activator from Streptococcus uberis. J Bacteriol 2002 Jan;184(1):119-25.
- Schroeder B, Boyle MD, Sheerin BR, Asbury AC, Lottenberg R. Species specificity of plasminogen activation and acquisition of surface-associated proteolytic activity by group C streptococci grown in plasma. Infect Immun 1999 Dec;67(12):6487-95.
- Caballero AR, Lottenberg R, Johnston KH. Cloning, expression, sequence analysis, and characterization of streptokinases secreted by porcine and equine isolates of Streptococcus equisimilis. Infect Immun 1999 Dec;67(12):6478-86.
- Frank C, Steiner K, Malke H. Conservation of the organization of the streptokinase gene region among pathogenic streptococci. Med Microbiol Immunol 1995 Oct;184(3):139-46.
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