Molecular stability of Hb Philly (alpha 2 beta 2 35(Cl) Tyr leads to Phe). Rhe relationship of hemoglobin stability to ligand state as defined by heat and mechanical shaking tests.

The molecular stability of Hb Philly (alpha 2 beta 2 35(Cl) Tyr leads to Phe) with different ligand states was compared with that of Hb A and Hb S using mechanical shaking and heat stability tests. The rates of mechanical denaturation of the oxy-forms of these hemoglobins decreased in the order of Hb S, Hb Philly, and Hb A, with relative ratios of 9.5: 5.6: 1.0. Upon oxidation to the met-forms, Hb Philly became mechanically most unstable, with ratios of 13.3: 23.0: 1.8, respectively. The deoxy-forms, of Hb A and Hb S were very stable, while that of Hb Philly was as unstable as the oxy-form. The addition of inositol hexaphosphate (IHP) to deoxy-Hb Philly stabilized the molecules. Since IHP restores the cooperative oxygen binding of Hp Philly, deoxy-Hb Philly appears to combine with IHP to change the quaternary structure required for cooperative oxygen binding and for stabilization of the molecule.

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