The effect of divalent cations on the conformation and function of human plasminogen.
The activation of native human plasminogen (Glu1-Pg) by tissue plasminogen activator, urinary plasminogen activator (u-PA), and streptokinase is inhibited by the divalent cations Ca2+, Mg2+, and Mn2+. This inhibition is accompanied by a conformational change in the molecule as evidenced by a decrease in Stokes' radius and intrinsic fluorescence. Kinetic analysis indicates that Mn2+ acts as an uncompetitive inhibitor of u-PA-catalyzed Glu1-Pg activation. In contrast to the inhibitory effects of divalent cations on Glu1-Pg, Ca2+ and Mg2+ stimulate the activation of proteolytically modified Lys77-Pg. These observations provide further evidence that Glu1-Pg and Lys77-Pg exhibit differential responses to ligands in the microenvironment.
Stack
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Department of Pathology, Duke University, Durham, North Carolina 27710.
Gonzalez-Gronow
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Pizzo
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D002413:Cations, Divalent / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005971:Glutamates / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008239:Lysine / Q000737:chemistry; D010958:Plasminogen / Q000378:metabolism*; D011487:Protein Conformation / Q000187:drug effects; D013050:Spectrometry, Fluorescence; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D002413:Cations, Divalent; D005971:Glutamates; D010958:Plasminogen; D014568:Urokinase-Type Plasminogen Activator; D008239:Lysine