Role of the His64 residue on the properties of the Fe-CO and Fe-O2 bonds in myoglobin.: A CHARMM/DFT study

Recent work on the structure and dynamics of the Fe-CO and Fe-O-2 bonds in carbonmonoxy myoglobin (MbCO) and oxymyoglobin (MbO(2)), respectively, is summarized. The calculations are performed by means of a hybrid QM/MM method based on Density Functional Theory (DFT) combined with the CHARMM force-field (J. Chem. Phys. 1999, 110, 10452). The results shed light into the long standing question of whether the myoglobin discriminates the CO ligand with respect to O-2 by distorting the FeCO bond. It is shown that both in the gas phase and in the protein the Fe-CO bond is essentially linear and therefore the hypothesis that the CO in MbCO is sterically hindered is excluded. In contrast, hydrogen bonding between the O-2 ligand and the His64 residue easily explains the protein discrimination for CO. (C) 2003 Elsevier B.V. All rights reserved.