Myoglobin and CO: structure, energetics, and disorder

The physiological significance of steric inhibition of CO binding to heme proteins is a fundamentally quantitative issue, since it has meaning only relative to the enhancement of O-2 binding by the protein. Previously, difficulties in reconciling structural and energetic data have hindered a quantitative assessment of the energetic cost of distorting the bound CO. Recent progress on both fronts suggests that the energetic cost of CO distortion in myoglobin is quite small. However, distortion of the surrounding protein to accommodate the heme-CO complex may contribute significantly to the free energy of CO binding. Polarized IR measurements on single crystals of MbCO not only yield precise structural information on the CO geometry, but also address the limitations of conventional structural refinement by characterizing conformational disorder in the crystalline state.