Discrimination between CO and O2 in Heme Oxygenase: Comparison of Static Structures and Dynamic Conformation Changes following CO Photolysis

Heme oxygenase (HO) catalyzes heme degradation, one of its products being carbon monoxide (CO). It is well known that CO has a higher affinity for heme iron than does molecular oxygen (O2); therefore, CO is potentially toxic. Because O2 is required for the HO reaction, HO must discriminate effectively between CO and O2 and thus escape product inhibition. Previously, we demonstrated large conformational changes in the heme–HO-1 complex upon CO binding that arise from steric hindrance between CO bound to the heme iron and Gly-139. However, we have not yet identified those changes that are specific to CO binding and do not occur upon O2 binding. Here we determine the crystal structure of the O2-bound form at 1.8 Å resolution and reveal the structural changes that are specific to CO binding. Moreover, difference Fourier maps comparing the structures before and after CO photolysis at