Rates of evolution of pyridoxal-5 '-phosphate-dependent enzymes

The pyridoxal-5'-phosphate-dependent enzymes (B-6 enzymes), that operate in the metabolism of amino acids, are of multiple evolutionary origin. To est imate their rates of evolution, a total of 180 sequences of 21 B-6 enzymes from distantly related eukaryotic species were compared. The enzymes belong to all four evolutionarily independent families of B-6 enzymes with differ ent folds, i.e., the large a family, the beta family, the D-alanine aminotr ansferase family, and the alanine racemase family. Their unit evolutionary periods, i.e., the time for a 1% sequence difference to accumulate between branches, ranged from 4.6 to 45.1 million years. Both, fastest changing ser ine pyruvate aminotransferase and most slowly changing glutamate decarboxyl ase are members of the a family. The evolutionary rates of the few enzymes belonging to the other three families were interspersed among those of the a family members. Enzymes that catalyze the same reaction, e.g., transamina tion or amino acid decarboxylation, with different substrates show widely v arying rates. The absence of correlations of the rate of evolution with eit her protein fold or type of catalyzed reaction suggests that individual fun ctional constraints have determined the differential rates of evolution of B-6 enzymes. (C) 2000 Academic Press.