Hydroxylysine, collagen structure

Vitamin C is essential for the formation of collagen, the principal structural protein in skin, bone, tendons, and ligaments, being a cofactor in the hydroxylation of the amino acids proline to 4-hydroxyproline, and of lysine to 5-hydroxylysine. These hydroxyamino acids account for up to 25% of the collagen structure. Vitamin C is also associated with some other hydroxylation reactions, e.g. the hydroxylation of tyrosine to dopa (dihydroxyphenylalanine) in the pathway to catecholamines (see Box 15.3). Deficiency leads to scurvy, a condition characterized by muscular pain, skin lesions, fragile blood vessels, bleeding gums, and tooth loss. Vitamin C also has valuable antioxidant properties (see Box 9.2), and these are exploited commercially in the food industries. 

Hydroxyproline and hydroxylysine Collagen contains hydroxy proline (hyp) and hydroxylysine (hyl), which are not present in most other proteins. These residues result from the hydroxylation of some of the proline and lysine residues after their incorporation into polypeptide chains (Figure 4.6). The hydroxylation is, thus, an example of posttranslational modification (see p. 440). Hydroxy proline is important in stabilizing the triple-helical structure of colla gen because it maximizes interchain hydrogen bond formation. 

The many (possibly more than 30) types of collagens found in human connective tissues have substantially the same chemical structure consisting mainly of glycine with smaller amounts of proline and some lysine and alanine. In addition, there are two unusual amino acids, hydroxyproline and hydroxylysine, neither of which has a corresponding base-triplet or codon within the genetic code. There is therefore, extensive post-translational modification of the protein by hydroxylation and also by glycosylation reactions. 

Although the exact amino acid sequence differs between the various collagens, the primary structure usually conforms to a repeating tripeptide Gly-X-Y where X and Y are, proline, lysine, or hydroxyproline, hydroxylysine respectively. A single unit of collagen is a triple helix composed of three a chains. This conformation differs from the common a helix found in proteins in two important ways ... 

In collagen, hydroxyproline stabilizes the triple helix structure by forming hydrogen bonds via water between adjacent chains or regions of the same chain. Hydroxylysine provides sites for glycosylation of proteins, and is essential for stabilization of intermolecular cross-links formed by reaction between lysine or hydroxylysine aldehyde and the e-amino group of lysine or hydroxylysine. 

Another example of a peptide sequence in a protein forcing it into a biologically useful conformation is found with collagen. This consists of a triple helix with chains of more than 1000 amino-acid residues, many of which are post-translation-ally modified. The latter steps, consisting inter alia of hydroxylation of Pro and Lys residues and 5-hydroxylysine residues, occur before the triple helix is formed, because the enzymes involved do not act on the helical structure. When the individual peptide chains of collagen are synthesised, there are N- and C-terminal sequences each containing about 100 amino-acid residues. These sequences favour the formation of a triple helix. When this has been achieved, the terminal sequences are removed. The sequences of these temporary terminal sequences are quite different from the main body of the collagen monomers, which consists of triads of the type Gly—X—Y, where X and Y are often proline or 3- or 4-hydroxyproline. 

Connective tissue between cells is made from the protein collagen. Collagen has a unique triple-helix structure requiring several modified amino acids, including hydroxyproline and hydroxylysine. 

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