Schematic representation of the apolar channel site corresponding to the free energy well for oxygen migration, which is ∼5 Å from the iron in wt Mb. In the left panel, His-E7 is in the closed conformation, perturbing the well, whereas in the right panel, it is open, leaving the well unrestricted for oxygen entry. Heme group (yellow) with iron atom (green) and relevant E7, E10 and E11 residues (cyan) are shown explicitly. The arrow indicates the small lateral movement that the His-E7 side chain and the E helix undergo to allow oxygen to migrate toward the iron in the closed conformation.