Proton nuclear magnetic resonance studies on hemoglobin malmo: implications of mutations at homologous positions of the α and β chains

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Abstract
The abnormal human Hb Malmo (.beta.97FG4 His .fwdarw. Gln) was studied and its properties compared with those of normal adult Hb A. The ring-current shifted proton resonances of both HbCO and HbO2 Malmo were very different from the corresponding forms of Hb A. The hyperfine shifted proton resonances of deoxy-Hb Malmo did not differ drastically from those of deoxy-Hb A. This result, together with the finding that the exchangeable proton resonances of the deoxy form of the 2 Hb were similar, suggests that unliganded Hb Malmo can assume a deoxy-like quaternary structure both in the absence and presence of organic phosphates. The properties of Hb Malmo were compared with those of Hb Chesapeake (.alpha.92FG4 Arg .fwdarw. Leu). The mutation at .beta.FG4 apparently has its greatest effect on the tertiary structure of the heme pocket of the liganded forms of the Hb while the mutation at .alpha.FG4 altered the deoxy structure of the Hb molecule but did not alter the tertiary structure of the heme pockets of the liganded form of the Hb molecule. Both Hb underwent transition from the deoxy (T) to the oxy (R) quaternary structure upon ligation. The abnormally high O2 affinities and low cooperativities of these 2 Hb must therefore be due to either the structural differences and/or to an altered transition between the T and R structures.