Hydroxyproline is produced by hydroxylation of the amino acid proline by the enzyme prolyl 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.[2]
Hydroxyproline is a major component of the proteincollagen,[3] comprising roughly 13.5% of mammalian collagen. Hydroxyproline and proline play key roles for collagen stability.[4] They permit the sharp twisting of the collagen helix.[5] 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.[6] 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.[7]
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.[2]
Other hydroxyprolines also exist in nature. The most notable ones are 2,3-cis-, 3,4-trans-, and 3,4-dihydroxyproline, which occurs in diatomcell walls[11] and are postulated to have a role in silica deposition. Hydroxyproline is also found in the walls of oomycetes, fungus-like protists related to diatoms.[12] (2S,4S)-cis-4-Hydroxyproline is found in the toxic cyclic peptides from Amanita mushrooms (e.g., phalloidin).[13]
^R.H.A. Plimmer (1912) [1908]. R.H.A. Plimmer; F.G. Hopkins (eds.). The chemical composition of the proteins. Monographs on biochemistry. Vol. Part I. Analysis (2nd ed.). London: Longmans, Green and Co. p. 132. Retrieved January 18, 2010.
^Nelson, D. L. and Cox, M. M. (2005) Lehninger's Principles of Biochemistry, 4th Edition, W. H. Freeman and Company, New York.
^Brinckmann, J., Notbohm, H. and Müller, P.K. (2005) Collagen, Topics in Current Chemistry 247, Springer, Berlin.
^Bella, J; Eaton, M; Brodsky, B; Berman, HM (1994). "Crystal and molecular structure of a collagen-like peptide at 1.9 A resolution". Science. 266 (5182): 75–81. doi:10.1126/science.7695699. PMID7695699.
^Alexopoulos, C.J., Mims C.W. and Blackwell, M. (1996). Introductory Mycology (4th ed.). New York: John Wiley & Sons. pp. 687–688. ISBN978-0-471-52229-4.{{cite book}}: CS1 maint: multiple names: authors list (link)
^Wieland, T. (1986). Peptides of Poisonous Amanita Mushrooms. Springer.
