Hydroxylation of Proline and Lysine Residues in Collagens and Other Animal and Plant Proteins

4-Hydroxyproline, 3-hydroxyproline and hydroxylysine (Figure 1) are found in animals almost exclusively in collagens and a few other extracellular proteins with collagen-like amino acid sequences. 4-Hydroxyproline is also found in plants, primarily in a family of cell-wall glycoproteins, the best studied among which are the extensins. All three amino acids are formed as cotranslational and posttranslational modifications by the hydroxylation of peptide-bound proline or lysine residues by three separate enzymes, prolyl 4-hydroxylase (EC 1.14.11.2, procollagen-proline, 2-oxoglutarate 4-dioxygenase), prolyl 3-hydroxylase (EC 1.14.11.7, procollagen-proline, 2-oxoglutarate 3-dioxygenase), and lysyl hydroxylase (EC 1.14.11.4, procollagen-lysine, 2-oxoglutarate 5-dioxygenase). Prolyl 4-hydroxylase is widely distributed in nature, as it has now been identified in a number of vertebrate, invertebrate, and plant sources. The two other enzymes are also found in a variety of animal sources, but they appear to be absent from plants.