A recombinant. protein, Schistosoma japonicum glutathione-S-transferase (SjGST), was fused with a C-terminal hexa-histidine tag to obtain SjGST/His. Both proteins were used to probe the interaction mechanisms with the metal ions immobilized on chromatography gels. Isothermal titration calorimetry was used to directly measure the adsorption enthalpies (DeltaH(ads)) of both proteins with Ni-NTA and TALON (Co2+) commercial affinity resins, under the conditions of with and without the presence of a denaturant. The result reveals that SjGST/His had a lower DeltaH(ads) value with Ni-NTA than did SjGST, mainly attributed to the formation of more coordination bonds with or a stronger binding with Ni-NTA. Furthermore, the difference between the DeltaH(ads) values of SjGST/His onto TALON under the nature and denaturing conditions were insignificant, implying that the binding topography of the hexa-histidine tail with immobilized Co2+ was not significantly changed with the presence of a denaturant. In addition, this study shows that the proposed binding models and the directly measured adsorption heat can be combined to elucidate the difference in the interaction mechanisms of SjGST/His adsorption onto those two adsorbents from a thermodynamic perspective.