Left, a schematic representation of an evolutionary transition from Anc4 to Anc5. Crystal structures of Anc4 and Anc5 solved to 1.13 A and 1.57 A, respectively. Right, structural superimposition of Anc4 and Anc5. Two catalytic glutamic acids and one serine reside that holds catalytic water are indicated as magenta spheres. 45 substitution residues are indicated as purple spheres.