Movements at the hemoglobin A-hemes and their role in ligand binding, analyzed by X-ray crystallography

The two hemoglobin structures determined by Max Perutz, the liganded R-state, which has high oxygen affinity, and the unliganded T-state with low oxygen affinity, were landmarks in molecular and structural biology (Perutz and Lehman, Nature 1968, 219, 902-909; Bolton and Perutz, Nature 1970, 28, 551-552; Perutz et al., Nature 1968, 219, 131-139). They provided the basis of a structural mechanism that connected beautifully to the theory of cooperativity in protein systems, formulated at about the same time by Monod et al. (J Mol Biol 1965, 12, 88-1118). Over the last 40 years there have been extensive biochemical and structural studies on hemoglobin's structure and the mechanisms that govern its co-operativity, specificity, and other physiological properties. There are still however a number of unresolved issues over the molecule's properties, for example the mechanism responsible for the affects of pH on oxygen affinity, i.e., the Bohr and Root effects. In this communication the differences in the geometry at the a-heme of unliganded and liganded human and the Antarctic fish (Trematomus) hemoglobin will be described and their relevance to affinity considered.