Structure of inositol hexaphosphate–human deoxyhaemoglobin complex

Abstract

D-2,3-DIPHOSPHOGLYCERATE (DPG) facilitates the transfer of oxygen from human red blood cells to the tissues by lowering the oxygen affinity of haemoglobin¹. It does so by combining preferentially with one of the two alternative forms of haemoglobin, namely the deoxy form, in the ratio of 1 mol per mol tetramer. Its binding site was predicted from biochemical and model building experiments and then determined directly by X-ray crystallography². The site lies at the entrance to the central cavity between the N-termini of the β chains and is surrounded by four pairs of basic groups: the α amino group of valine 1 and the side chains of histidines 2 and 143, and of lysine 82. The basic groups are related in pairs by the molecular dyad and arranged so as to complement the acidic groups of DPG by forming seven salt bridges (Fig. 1). On oxygenation the N-termini of the β chains move apart and the cavity closes up so that the stereochemical complementarity is lost³. Oxyhaemoglobin does also bind DPG, but much more weakly, and the binding site is still unknown.