The structure of metmanganoglobin, in which Mn(III) replaces Fe(III) as the heme metal, has been compared with that of native hemoglobin by X-ray difference Fourier techniques. Their quaternary structures are identical and their tertiary structures are similar, as expected both from the close stereochemical correspondence between manganese porphyrins and the corresponding iron porphyrins, and from the similarities in functional properties previously reported. There are, however, a number of small but significant differences. The α-heme is essentially unperturbed by the metal substitution, in contrast to the β-heme. It appears that the sixth ligand of the β-heme, a water molecule in native hemoglobin, has been lost, and that the resultant five-co-ordinate β-heme in metmanganoglobin is distinctly ruffled in accord with quasi-S4 symmetry. The loss of non-covalent ligand-globin interactions together with the heme ruffling produce numerous small perturbations in the β-globin, which are transmitted across the α1-β1 interface to the α-globin. The α1-β2 interface is only slightly perturbed. Metmanganoglobin thus displays some, but not all, of the structural features to be expected in a partially liganded hemoglobin: those arising directly from ligand loss from the β-hemes, and contraction of the ligand pocket in the β-chain, but not others, such as those which accompany a marked alteration in the distance of the proximal histidine from the mean plane of the porphyrin. The basic similarity in the structural and functional properties of manganoglobin and native hemoglobin demonstrates that hemoglobin function is not uniquely dependent on the co-ordination properties of the metal.
ASJC Scopus subject areas
- Molecular Biology