Zinc ions promote the interaction between heparin and heparin cofactor II

The effects of bivalent cations on heparin binding, structure, and thrombin inhibition rates of heparin cofactor II were examined. Zn(2+) - and to a lesser extent Cu(2+) and Ni(2+) - enhanced the interaction between heparin cofactor II and heparin as demonstrated by heparin affinity chromatography and surface plasmon resonance experiments. Metal chelate chromatography and increased intrinsic protein fluorescence in the presence of Zn(2+) indicated that heparin cofactor II has metal ion-binding properties. The results are compatible with the hypothesis that Zn(2+) induces a conformational change in heparin cofactor II that favors its interaction with heparin.