The role of carbohydrate in the activation of plasminogen 2 glycoforms by streptokinase

Plasminogen 2 has six glycoforms that differ in their sialic acid content. In this study we have examined the effect that this differential sialylation has on activation of these glycoforms by streptokinase (SK). We find that increases in sialic acid content, above a threshold level, result in a decrease in the catalytic efficiency of activation. This decrease in catalytic efficiency appears to be due to an increase in K(m) values and a decrease in K(cat) values. This phenomenon is most apparent in the activation of plasminogen 2∅, the most extensively sialylated glycoform with 13 mols of sialic acid/mol protein. Gel filtration demonstrated that SK forms an activator complex with plasminogen 2∅, indicating that the carbohydrate on plasminogen 2 interferes with the stability of the Michaelis complex, rather than the ability of streptokinase to form activator complexes with plasminogen 2 glycoforms. For comparison we also show data pertaining to activation of plasminogen 2 glycoforms by urinary plasminogen activator and tissue-type plasminogen activator.