MYOGLOBIN (Mb) consists of a single polypeptide chain of 153 residues and one haem. It combines reversibly with molecular oxygen which it takes up from the blood and passes on to mitochondria in muscle. In vivo its iron atom remains ferrous, but in vitro it autoxidises to the ferric metmyoglobin (metmb) in which the sixth ligand at the iron is water. Metmb of sperm whale was the first protein structure to be determined1. Takano recently determined the closely related structure of deoxymb by X-ray analysis, while that of COmb has been determined by neutron diffraction (refs 2, 3 and B. P. Schoenborn, personal communication). The most interesting structure, that of oxymb, has proved elusive. Watson and Nobbs tried to determine it by rapid crystallisation and collection of X-ray data at 4 °C, but even so autoxidation obscured the results4. Recent advances in low temperature techniques encouraged me to try again, especially in view of the wide interest in the nature of the iron−oxygen bond5−7.
Myoglobin contains a porphyrin ring with an iron center. There is a proximal histidine group attached directly to the iron center, and a distal histidine group on the opposite face, not bonded to the iron.
Many functional models of myoglobin have been studied. One of the most important is that of picket fence porphyrin by James Collman. This model was used to show the importance of the distal prosthetic group. It serves three functions:
1. To form hydrogen bonds with the dioxygen moiety, increasing the O2 binding constant
2. To prevent the binding of carbon monoxide, whether from within or without the body. Carbon monoxide binds to iron in an end-on fashion, and is hindered by the presence of the distal histidine, which forces it into a bent conformation. CO binds to heme 23,000 times better than O2, but only 200 times better in hemoglobin and myoglobin. Oxygen binds in a bent fashion, which can fit with the distal histidine.
3. To prevent irreversible dimerization of...