Abstract

Vertebrate haemoglobin (Hb), the oxygen‐carrying protein of the blood, consists of two α‐ and two β‐subunits, each containing one haem, and shows cooperative oxygen binding known as the haem–haem interaction. The amino‐acid sequences of Hbs found in different species have diverged considerably and the homology in the most distantly related ones is only 40%. How can such varied amino‐acid sequences give rise to similar three‐dimensional structures and functional properties? To what extent do amino‐acid replacements affect the structure of haemoglobin? Which mutations are responsible for the functional differences between haemoglobins from different species? Expression of α‐ and β‐globins in Escherichia coli has enabled us to introduce any mutations in the haemoglobin molecule at will. By X‐ray crystallographic and functional studies of the engineered mutants, we are trying to answer these questions.