Crystal structure of nickel reconstituted hemoglobin - a case for permanent T-state hemoglobin

Abstract

The three-dimensional crystal structure of nickel-re constituted human haemoglobin (NiHb) is determined by X-ray crystallography at 2.5 Å resolution. The final refined model, when compared with deoxy haemoglobin, clearly reveals a permanent T-state conformation of NiHb. The tertiary changes asoociated with the alpha subunit are larger in magnitude than those in beta subunits. However, there are some significant quaternary changes observed at the interfacial regions arising out of the perturbations associated with the Ni haeme in the alpha subunit. The central metal ion in the two alpha subunits and one of the beta subunits is clearly four-coordinated, while the other beta subunit reveals a greater tendency for the metal ion to be five-coordinated at the heme site. This result is consistent with the earlier findings like optical resonance Raman, NMR, and spin-labelled EPR studies on NiHb, which show two different metal ion environments in NiHb, interpreted as due to four and five-coordination. Hence it is clear that there is in-equivalence between the two beta subunits in addition to the heterogeneity observed among the alpha and beta subunits. Crystallographic evidence revealing the presence of a five-coordinated nickel(II) porphyrin complex is a special feature of interest presentes here.