Relation between hen egg white lysozyme and bacteriophage T4 lysozyme: Evolutionary implications

Hen egg white lysozyme and T4 bacteriophage lysozyme have the same catalytic function, but have non-homologous amino acid sequences. Notwithstanding the differences in their primary structures, the two lysozymes have similarities in their overall backbone conformations, in their modes of binding substrates and probably in their mechanisms of action. By different criteria, the similarity between the folding of the two enzymes can be shown to be statistically significant. Also the transformation which optimizes the agreement between the backbones of the two molecules is shown to accurately align their active site clefts, so that saccharide units bound in the A, B, C and D subsites of hen egg white lysozyme coincide within 1 to 2 Å with analogous saccharides bound to phage lysozyme. Furthermore, a number of the specific interactions between enzyme and substrate which were observed for hen egg white lysozyme, and thought to be important for catalysis, are found to occur in a structurally analogous way in the phage enzyme. Fifty-four atoms from the respective active sites which appear to be equivalent, including saccharides bound in the B and C sites, superimpose with a root-mean-square discrepancy of 1.35 Å. These structural and functional similarities suggest that the two lysozymes have arisen by divergent evolution from a common precursor. This is the first case in which two proteins of completely different amino acid sequence have been shown, with high probability, to have evolved by divergent rather than convergent evolution.