Molecular evolution of pyridoxal-5′-phosphate-dependent enzymes

Summary

The pyridoxal-5′-phosphate-dependent enzymes (B₆ enzymes) that act on amino acid substrates are of multiple evolutionary origin. Database searches with sequence profiles indicate that the B₆ enzymes can be subdivided into several families of homologous proteins of which the α family is by far the largest. The α family includes enzymes that catalyze, with few exceptions, transformations of amino acids in which the covalency changes are limited to Cα. Enzymes of the β or γ families mainly catalyze replacement and elimination reactions at Cβ or Cγ, respectively. Apparently, the primordial pyridoxal-5′-phosphate-dependent enzymes were regio-specific catalysts, which first specialized for reaction specificity and then for substrate specificity. Part of the amino acid decarboxylases belong to the α family, the other decarboxylases constitute three different evolutionarily independent families. A few other B₆ enzymes appear to represent additional families of B₆ enzymes.