Myoglobin models and steric origins of the discrimination between O 2 and CO

Abstract

Synthetic models of the myoglobin active site have provided much insight into factors that affect CO and O 2 binding in the proteins. "Capped" and "pocket" metal porphyrin systems have been developed to probe how steric factors affect ligand binding and ultimately to elucidate important aspects of the mechanism of CO discrimination in the proteins. These model porphyrins are among the most thoroughly characterized systems to date. From the twenty-one known crystal structures, analysis of the types of distortion that occur upon ligand binding under the cap, including porphyrin doming and ruffling, lateral and horizontal movement of the cap, and bending and tilting of the Fe–C–O bond, provides an indication of how steric interactions will affect structure in Hb and Mb. The model porphyrin systems discussed range from those that discriminate against O 2 binding compared to biological systems to those with similar CO and O 2 binding strength to myoglobin, and also to those that bind both O 2 and CO very weakly or not at all. The primary type of distortion observed upon CO binding is vertical or lateral movement of the cap and some ruffling of the porphyrin plane. Minimal bending or tilting of the M–C–O bond is observed, suggesting that the Fe–C–O bending that has been found from crystal structures of the hemoproteins is unlikely.