Is the CO adduct of myoglobin bent, and does it matter?

Early reports of a severely bent CO adduct in myoglobin inspired the idea t hat heme proteins discriminate against CO, relative to O-2, via steric hind rance imposed by a distal histidine residue. Recent results showing that th e bound CO is only slightly distorted do not by themselves overthrow the st eric hypothesis, because the steric energy could be stored in displacements of the protein. However, experimental data on site-directed mutants show t hat the main determinant of ligand affinity changes is the polarity of the binding pocket and that H-bonding by the distal histidine accounts for abou t 85% of the O-2/CO discrimination while steric hindrance accounts for the remaining 15%.