Three-dimensional structure of staphylokinase, a plasminogen activator with therapeutic potential

@article{Rabijns1997ThreedimensionalSO,
  title={Three-dimensional structure of staphylokinase, a plasminogen activator with therapeutic potential},
  author={Anja Rabijns and Hendrik L. De Bondt and Camiel J. De Ranter},
  journal={Nature Structural Biology},
  year={1997},
  volume={4},
  pages={357-360}
}
The three-dimensional structure of staphylokinase has been determined at 1.8 A. The puntative site of interaction with plasminogen was identified and epitopes were mapped. 
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Pro42 and Val45 of staphylokinase modulate intermolecular interactions of His43–Tyr44 pair and specificity of staphylokinase–plasmin activator complex
Design of a novel plasminogen activator based on the structure of hirudin.
TLDR
In vitro assay demonstrated that this hirudin-like fusion protein can activate human plasminogen and retain the function of thrombin inhibition and a significant functional improvement might originate from a more specific active structure due to the hirUDin scaffold.
Crystal structure of a staphylokinase: variant a model for reduced antigenicity.
TLDR
X-ray crystallographic evidence that the SAK(S41G) mutant may assume a dimeric structure is presented and several potential mutation sites at the dimer interface are proposed that may further reduce the antigenicity of SAK.
Intermolecular interactions in staphylokinase–plasmin(ogen) bimolecular complex: Function of His43 and Tyr44
Use of the plasminogen activation system by microorganisms.
NH2-terminal Structural Motifs in Staphylokinase Required for Plasminogen Activation*
TLDR
It is suggested that a positively charged amino acid in the ultimate or penultimate NH2-terminal position corresponding to amino acids 11–16 of this flexible region participates in the reconfiguration of the active site of theplasmin molecule to endow it with plasminogen-activating potential.
Staphylokinase has distinct modes of interaction with antimicrobial peptides, modulating its plasminogen-activation properties
TLDR
Overall, this work identifies two distinct AMP binding surfaces on SakΔN10 whose occupation would lead to either inhibition or promotion of its plasminogen activating properties.
Construction and characterization of novel staphylokinase variants with antiplatelet aggregation activity and reduced immunogenecity.
TLDR
It is confirmed that it is possible to design and produce a bifunctional protein that possesses fibrinolytic and antiplatelet aggregation activities and the immunogenicity of the variants was greatly reduced.
Human plasminogen catalytic domain undergoes an unusual conformational change upon activation.
Activation of the serine protease plasmin from its zymogen, plasminogen, is the key step in fibrinolysis leading to blood clot dissolution. It also plays critical roles in cell migration, such as in…
Crystal structure of the catalytic domain of human plasmin complexed with streptokinase.
TLDR
The crystal structure of streptokinase complexed with the catalytic unit of human plasmin was solved and the amino-terminal domain of strePTokinase in the complex is hypothesized to enhance the substrate recognition.
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References

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Staphylokinase: an Activator of Plasma Protease
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  • Medicine, Biology
    Nature
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SEVERAL workers1 have reported the lysis of fibrin clots by staphylococci, and this has been assumed to be due to a fibrinolysin produced by the bacteria.
Physical and conformational properties of staphylokinase in solution.
On the mechanism of the activation of human plasminogen by recombinant staphylokinase.
On the mechanism of fibrin-specific plasminogen activation by staphylokinase.
Crystallization and preliminary X‐Ray analysis of recombinant staphylokinase
Diffraction quality crystals of recombinant staphylokinase (STAR) have been grown by the hanging drop vapor diffusion technique from a solution containing MgCl2, Tris buffer (pH 8.5), and…
Structure-Function Relationships in Staphylokinase as Revealed by "Clustered Charge to Alanine" Mutagenesis (*)
TLDR
Findings support a mechanism for the activation of plasminogen by SakSTAR involving formation of an equimolar complex of SakSTAR with traces of plAsmin, which converts pl asminogen to plasmini and, more rapidly, inactive plasmineogen-SakSTAR to plAsMin-SAKSTAR.
The thermostability of natural variants of bacterial plasminogen-activator staphylokinase.
TLDR
Three natural variants of staphylokinase have a different sensitivity to thermal inactivation, that is mediated by reversible unfolding of the protein and concentration-dependent irreversible aggregation, which would facilitate its development for clinical use.
Functional properties of recombinant staphylokinase variants obtained by site-specific mutagenesis of methionine-26.
Isolation and conditioning of recombinant staphylokinase for use in man
Similarity of three-dimensional structure between the immunoglobulin domain and the copper, zinc superoxide dismutase subunit.
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