| Abstract: | Of the 85 three-dimensionally characterized residues of cytochrome b5, 51 are found to be structurally and topologically equivalent to the globin fold. When these proteins have been superimposed, the heme irons are found to be less than 1.4 A separated and the heme normals are inclined by less than 9.5 degrees. The proximal histidine of the globins and two adjacent helices are equivalent to the sixth iron ligand and adjacent helices of cytochrome b5. Larger differences in structure are observed on the distal side of the heme, coincident with the most changeable part of the globin structures. The heme itself is rotated by 53 degrees about its normal but such a change is energetically minimal and conservative as the heme side groups are not directly involved in the function of the molecules. The beta-sheet of cytochrome b5 is inserted into a corresponding cavity of the globins forming an additional lining to the heme pocket. The roughly 50 residues missing at the carboxy end of the known cytochrome b5 fragment could correspond in part to the H helix in the globins. While it would seem probable that these similarities represent divergent evolution from a primordial heme-binding protein, the possibility of structural convergence to a functionally satisfactory protein cannot be excluded. |
