title: The effect of divalent cations on the conformation and function of human plasminogen.
abstract: 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.
authors.affiliation: Department of Pathology, Duke University, Durham, North Carolina 27710.
authors.forename: S
authors.initials: S
authors.lastname: Stack
authors.forename: M
authors.initials: M
authors.lastname: Gonzalez-Gronow
authors.forename: S V
authors.initials: SV
authors.lastname: Pizzo
mesh_terms: 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
chemical_list: D002413:Cations, Divalent; D005971:Glutamates; D010958:Plasminogen; D014568:Urokinase-Type Plasminogen Activator; D008239:Lysine