Hydroxyproline is produced by
hydroxylation of the amino acid
proline by the enzyme
prolyl 4-hydroxylase following protein synthesis (as a
post-translational modification). The enzyme-catalyzed reaction takes place in the
lumen of the
endoplasmic reticulum. Although it is not directly incorporated into proteins, hydroxyproline comprises roughly 4% of all amino acids found in animal tissue, an amount greater than seven other amino acids that are translationally incorporated.
Animals Collagen Hydroxyproline is a major component of the
protein collagen, comprising roughly 13.5% of mammalian collagen. Hydroxyproline and proline play key roles for collagen stability. They permit the sharp twisting of the collagen helix. In the canonical collagen Xaa-Yaa-Gly triad (where Xaa and Yaa are any amino acid), a proline occupying the Yaa position is hydroxylated to give a Xaa-Hyp-Gly sequence. This modification of the proline residue increases the stability of the collagen
triple helix. It was initially proposed that the stabilization was due to water molecules forming a hydrogen bonding network linking the prolyl hydroxyl groups and the main-chain carbonyl groups. It was subsequently shown that the increase in stability is primarily through
stereoelectronic effects and that hydration of the hydroxyproline residues provides little or no additional stability.
Non-collagen Hydroxyproline is found in few proteins other than collagen. For this reason, hydroxyproline content has been used as an indicator to determine
collagen and/or
gelatin amount. However, the mammalian proteins
elastin and
argonaute 2 have collagen-like domains in which hydroxyproline is formed. Some snail poisons,
conotoxins, contain hydroxyproline, but lack collagen-like sequences.
DYRK1A,
DYRK1B,
protein kinase B,
eEF2,
IKK2,
p53,
FOXO3A,
CEP192 are also reportedly hydroxylated by
PHD1. p53 and
MAPH6 are also hydroxylated by PHD3. These hydroxyprolines serve as the attachment points for
glycan chains which are added as
post-translational modifications.
Phytophthora cactorum specifically produces a pathogenic protein containg 4-hydroxyproline. == Catabolism ==