Mapping of the Antigenic Regions of Streptokinase in Humans after Streptokinase Therapy

Torréns, Isis; Reyes, Osvaldo; Ojalvo, Ariana G.; Seralena, Alina; Chinea, Glay; Cruz, Luis J.; Fuente, José de la

doi:10.1006/bbrc.1999.0747

Cited by 20 publications

(11 citation statements)

References 25 publications

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“…Although this loop region was mobile in the SK‐μPm complex, its relative location to the putative substrate binding site suggests its importance in the interaction with substrate plasminogen. The highly exposed position of this loop and its flexible conformation would explain its significant involvement in the immunogenicity of SK [25] and its possible induced‐conformational change upon binding to a substrate.…”

Section: Resultsmentioning

confidence: 99%

Crystal structure of streptokinase β‐domain

Wang¹,

Tang²,

Hunter³

et al. 1999

FEBS Letters

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Streptokinase, a 47 kDa secreted protein of hemolytic strains of streptococci, is a human plasminogen activator and contains three structural domains linked by flexible loops. We describe here the crystal structure of the isolated streptokinase middle (SKbeta) domain determined at 2.4 A resolution. Among the functionally important structural features is a putative binding site for a kringle domain of plasminogen located at the tip of a fully exposed hairpin loop. The distribution of genetically conserved residues of SKbeta is strongly correlated with their functions. The extensive interface of the SKbeta dimer suggests that such dimers may also exist in solution for free SKbeta.

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Section: Resultsmentioning

confidence: 99%

Crystal structure of streptokinase β‐domain

Wang¹,

Tang²,

Hunter³

et al. 1999

FEBS Letters

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“…High levels of circulating antistreptokinase antibodies reduce the effectiveness of repeat streptokinase therapy by rapidly neutralising streptokinase upon administration or by causing numerous allergic complications [98,99]. A number of antigenic regions have been identified within the streptokinase protein by using murine monoclonal antibodies or patient sera [100][101][102][103]. Targeting these regions with deletion or site directed mutagenesis has been proposed as possible mechanisms by which the immunogenicity of streptokinase can be reduced.…”

Section: Second Generation Thrombolytic Therapeutics Based On Streptomentioning

confidence: 99%

The Role of Streptokinase as a Virulence Determinant of Streptococcus pyogenes – Potential for Therapeutic Targeting

McArthur

Cook²,

Venturini³

et al. 2012

CDT

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. (2012). The role of streptokinase as a virulence determinant of streptococcus pyogenes -potential for therapeutic targeting. Current Drug Targets, 13 (3), 297-307. The role of streptokinase as a virulence determinant of streptococcus pyogenes -potential for therapeutic targeting AbstractStreptococcus pyogenes is a major human pathogen responsible for numerous diseases ranging from uncomplicated skin and throat infections to severe, life threatening invasive disease such as necrotising fasciitis and streptococcal toxic shock syndrome. These severe invasive infections progress rapidly and produce high rates of morbidity and mortality despite the implementation of aggressive treatment plans. The activation of plasminogen and the acquisition of plasmin activity at the bacterial cell surface is critical for the invasive pathogenesis of this organism. To facilitate this process, S. pyogenes secrete streptokinase, a potent plasminogen activating protein. Here, we describe the role of streptokinase in invasive pathogenesis and discuss some potentially useful strategies for disruption of streptokinase mediated plasminogen activation which could be employed to treat severe invasive S. pyogenes infections. AbstractStreptococcus pyogenes is a major human pathogen responsible for numerous diseases ranging from uncomplicated skin and throat infections to severe, life threatening invasive disease such as necrotising fasciitis and streptococcal toxic shock syndrome.These severe invasive infections progress rapidly and produce high rates of morbidity and mortality despite the implementation of aggressive treatment plans. The activation of plasminogen and the acquisition of plasmin activity at the bacterial cell surface is critical for the invasive pathogenesis of this organism. To facilitate this process, S. pyogenes secrete streptokinase, a potent plasminogen activating protein.Here, we describe the role of streptokinase in invasive pathogenesis and discuss some potentially useful strategies that disrupt streptokinase mediated plasminogen activation and could be employed to treat severe invasive S. pyogenes infections.3

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“…These findings have been confirmed by Torréns et al . [19] who, using peptide ladders, localized the minimal epitope of this region to between residues I1 and R10.…”

Section: Discussionmentioning

confidence: 99%

“…With the types of proteases available for this study it was not possible to determine which of these candidates constituted the actual epitope. However, Torréns et al [19] reported an epitope located between residues N170 and A189, and concluded that the most likely location of the epitope would be at residues P171–P177.…”

Section: Discussionmentioning

confidence: 99%

“…Their findings indicated that amino acids 3–7 were crucial in epitope formation. Recently, Torréns and coworkers [19] have mapped the antigenic regions using a cellulose‐bound synthetic peptide library of 20 amino‐acid SK fragments and whole patient sera. They reported common regions of antibody binding to be located at residues 1–20, 130–149, 170–189 and 390–399.…”

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confidence: 99%

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New antigenic regions of streptokinase are identified by affinity‐directed mass spectrometry

Coffey

Jennings

Dalton

2001

European Journal of Biochemistry

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Streptokinase (SK) is a bacterial protein used for the treatment of myocardial infarction, which is immunogenic in humans. Here we report the use of an affinity-directed MS approach to determine the minimal epitopes involved in the binding between SK and patient antibodies. Using this method we have identified two novel epitopes and mapped these to the minimal recognition regions formed by the amino acids D96-E99 and F323-D328. We have also located three previously identified antigenic regions and have now mapped them and shown that they can be defined more precisely as residues P4-L8, P171-P177 and K334-N338.

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Mapping of the Antigenic Regions of Streptokinase in Humans after Streptokinase Therapy

Cited by 20 publications

References 25 publications

Crystal structure of streptokinase β‐domain

Crystal structure of streptokinase β‐domain

The Role of Streptokinase as a Virulence Determinant of Streptococcus pyogenes – Potential for Therapeutic Targeting

New antigenic regions of streptokinase are identified by affinity‐directed mass spectrometry

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