Thermodynamic and kinetic aspects of metal binding to the histidine-rich protein, Hpn.

The histidine-rich protein, Hpn, binds to essential metals Ni2+, Cu2+, Zn2+ and a therapeutic metal Bi3+ with the in vitro affinities in the order of Cu2+ > Ni2+ > Bi3+ > Zn2+. In contrast, the in vivo (in E. coli) protection by the protein is in the order of Ni2+ > Bi3+ > Cu2+ approximately Zn2+. The release of Ni2+ from the protein follows a two-step process consisting of a rapidly established equilibrium and subsequently a rate-determining step (dissociation of Hpn-Ni...EDTA to Ni-EDTA). Our work suggests the nickel storage and homeostasis in H. pylori as the primary role of Hpn.