Drug-protein interactions: two-site binding of heterocyclic ligands to a monomeric hemoglobin.

The reactivity response of the heme proteins to the heterotropic effectors, purine, caffeine, theophylline, and (C2H5)4N+, have been examined. The heterotropic effectors influence the heme ligation affinities. The heme axial ligation of pyridine and pyrazole have not influenced the hemoglobin's affinity for caffeine and theophylline. The imidazole ligation indicates a mutual interaction between the heme active site and the noncoordinate binding site.