High-resolution crystal structure of magnesium (MgII)-iron (FeII) hybrid hemoglobin with liganded beta subunits.

The structures of deoxy (alpha(Mg(II))2 beta(Fe(II))2) and CO-liganded (alpha(Mg(II)2(Fe(II)-CO)2) forms of human hemoglobin were determined by X-ray crystallography to a resolution of 1.7 A and 1.9 A, respectively. The deoxy hybrid has virtually the same structure as that of the native deoxy HbA. Both the deoxy and CO-liganded hybrids assumed a T quaternary structure characteristic of native deoxy HbA. No significant structural difference was found between the alpha subunits of the CO-liganded hybrid and deoxy HbA, while in the beta subunit, significant tertiary structural changes were confined to the heme pocket. Baldwin showed by a comparison of COHbA and deoxy HbA that there is a 1.5 A shift of the beta subunit heme into its pocket. This shift was much reduced in alpha(Mg(II))2 beta(Fe(II)-CO)2. On the other hand, when the two structures are compared with superposition of hemes, the nearest neighbors of CO (Fe, E11 Val and E7 His) have shifted nearly to the same positions as those in COHbA. Thus the tertiary structure of the beta subunit of alpha(Mg(II))2 beta(Fe(II)-CO)2 is such that the CO molecule and the neighboring atoms assume nearly the same conformation as those of COHbA, while the block shift of these groups is impeded with respect to the structural invariant portions of the molecule.