Theoretical study of the discrimination between O2 and CO by myoglobin

Combined quantum chemical and molecular mechanics geometry optimisations have been performed on myoglobin without or with O-2 or CO bound to the haem group. The results show that the distal histidine residue is prolonated on the N-epsilon2 atom and forms a hydrogen bond to the haem ligand both in the O-2 and the CO complexes. We have also re-refined the crystal structure of CO-myoglobin by a combined quantum chemical and crystallographic refinement. Thereby, we probably obtain the most accurate available structure of the active site of this complex, showing a Fe-C-O angle of 171degrees, and Fe-C and C-O bond lengths of 170-171 and 116-117 pm. The resulting structures have been used to calculate the strength of the hydrogen bond between the distal histidine residue and O-2 or CO in the protein. This amounts to 31-33 kJ/mol for O-2 and 2-3 kJ/mol for CO. The difference in hydrogen-bond strength is 21-22 kJ/mol when corrected for entropy effects. This is slightly larger than the observed discrimination between O-2 or CO by myoglobin, 17 kJ/mol. We have also estimated the strain of the active site inside the protein. It is 2-4 kJ/mol larger for the 0, complex than for the CO complex, independent of which crystal structure the calculations are based on. Together, these results clearly show that myoglobin discriminates between O-2 and CO mainly by electrostatic interactions, rather than by steric strain. (C) 2002 Elsevier Science Inc. All rights reserved.