WILL THE REAL FECO PLEASE STAND UP

The paradigm that nature protects us from CO poisoning by forcing the bound CO to bend over in heme proteins, thereby reducing its binding a ffinity, is now in textbooks, but is nevertheless problematic. Results from vibrational spectroscopy give no evidence for bent CO, although X-ray crystallography continues to indicate appreciable distortions in myoglobin. However, the energetic significance of the discrepancy is doubtful, since new Density Functional Theory calculations indicate th at much less energy is required to distort the CO than had been though t, perhaps 2 kcal/mol or less. Binding studies on site-directed mutant s of myoglobin suggest that steric hindrance by the distal histidine i s worth ca. 1 kcal/mol. While the distal histidine does account for th e discrimination by Mb against CO and in favor of O-2, most of the eff ect is due to its H-bond with bound O-2.