Heme binding and polymerization by Plasmodium falciparum histidine rich protein II: influence of pH on activity and conformation

The histidine rich protein II (HRPII) from Plasmodium falciparum nm has bee n implicated as a heme polymerase which detoxifies free heme by its polymer ization to inactive hemozoin. Histidine-iron center coordination is the dom inant mechanism of interaction between the amino acid and heme, The protein also contains aspartate allowing for ionic/coordination interactions betwe en the carboxylate side chain and the heme metal center, The pH profile of heme binding and polymerization shows the possibility of these two types of binding sites being differentiated by pH, Circular dichroism studies of th e protein show that pH acid heme binding cause a change in conformation abo ve pH 6 implying the involvement of His-His+ transitions. Heme binding at p Hs above 6 perturbs HRPII conformation, causing an increase in helicity. (C ) 1999 Federation of European Biochemical Societies.