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

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