Molecular mechanisms of plasminogen activation: bacterial cofactors provide clues.
Plasminogen activation is a key event in the fibrinolytic system that results in the dissolution of blood clots, and also promotes cell migration and tissue remodelling. The recent structure determinations of microplasmin in complex with the bacterial plasminogen activators staphylokinase and streptokinase have provided novel insights into the molecular mechanisms of plasminogen activation and cofactor function. These bacterial proteins are cofactor molecules that contribute to exosite formation and enhance the substrate presentation to the enzyme. At the same time, they modulate the specificity of plasmin towards substrates and inhibitors, making a 'specificity switch' possible.
Parry
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MA
Max-Planck Institute of Biochemistry, Dept for Structural Research, Am Klopferspitz 18a, 82152 Martinsried, Germany.
Zhang
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XC
Bode
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I
D000595:Amino Acid Sequence; D005341:Fibrinolysin / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008666:Metalloendopeptidases / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D010958:Plasminogen / Q000737:chemistry / Q000378:metabolism*; D010960:Plasminogen Activators / Q000737:chemistry / Q000378:metabolism*; D013300:Streptokinase / Q000737:chemistry / Q000378:metabolism
D010446:Peptide Fragments; C054561:microplasmin; D010958:Plasminogen; D013300:Streptokinase; D010960:Plasminogen Activators; D005341:Fibrinolysin; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus