Structure of hemoglobin M Boston, a variant with a five-coordinated ferric heme

X-ray analysis of the natural valency hybrid alpha(2) (+M Boston)beta(2) (deoxy) shows that the ferric iron atoms in the abnormal alpha subunits are bonded to the phenolate side chains of the tyrosines that have replaced the distal histidines; the iron atoms are displaced to the distal side of the porphyrin ring and are not bonded to the proximal histidines. The resulting changes in tertiary structure of the alpha subunits stabilize the hemoglobin tetramer in the quaternary deoxy structure, which lowers the oxygen affinity of the normal beta subunits and causes cyanosis. The strength of the bond from the ferric iron to the phenolate oxygen appears to be the main factor responsible for the many abnormal properties of hemoglobin M Boston.