Structure-function relationships in the growing hexa-coordinate globin sub-family

Hemoglobin and related heme proteins reversibly bind gaseus diatomic ligands (O2, NO, CO) to a penta-coordinate heme Fe atom, the ligand filling the sixth coordination site. Several new globins have recently been reported to display a functionally-relevant hexacoordinate (6C) heme Fe atom, whose sixth coordination site is filled by an endogenous His protein ligand. The reversible intramolecular hexa- to penta-coordination process at the heme-Fe atom modulates O2, NO, CO ligand binding properties of 6C-globins. Here, we present the results of three-year investigations carried over in our lab on the crystal structures of 6C-hemoglobins from human brain, human tissues, and from Drosophila. Mechanisms for 6C-5C transitions are discussed on structural grounds.