Historically, Grishin et al (Protein Sci. 4, 1291) were the first to distinguish five different structural groups ('fold types') for pyridoxal-5'-phosphate dependent enzymes.
Fold types VI and VII were absent from the original subdivision proposed by Grishin et al., but we have adopted this denomination to classify structures which are unlike all other PLP-dependent enzymes.
Fold type I is by far the most common and variegated. It is typical of most aminotransferases and decarboxylases, but also includes enzymes that catalyze α, β or γ-eliminations.
Fold type II encompasses mainly enzymes which catalyze β-eliminations or replacements, such as L-serine ammonia lyase or tryptophan synthase.
Fold type III describes a subgroup of enzymes (such as alanine racemase and a subset of amino-acid decarboxylase) that bind PLP in the center of a (β/α)8 barrel structure. At present, we include in this fold also lysine-5,6-aminomutase because this protein, too, shows a (β/α)8 barrel structure, even though PLP is bound on the exterior, rather than on the interior, of the barrel (Berkovitch et al., 2004, Proc Natl Acad Sci U S A 101, 15870-5.).
Fold type IV includes D-amino acid aminotransferase and a few homologous enzymes.
Fold type V is so far only found in glycogen phosphorylases, enzymes that do not use PLP as an electrophilic catalyst, but rather employ the phosphate group of the cofactor to perform acid-base catalysis.
Finally, a fold type VI was absent from the original subdivision proposed by Grishin et al., but we have adopted this denomination to classify lysine-5,6-aminomutase - an enzyme that employs S-adenosyl-L-methionine (SAM) as a cofactor, in addition to PLP. Lepore et al (Proc Natl Acad Sci U S A 102, 13819-24) have recently reported the X-ray structure of lysine-2,3-aminomutase, showing a fold which is unlike all other PLP-dependent enzymes known to date, but partially analogous to other SAM-dependent enzymes.