Hydroxylation of lysine residues

In scurvy, defective collagen is produced because hydroxylation of procollagen does not occur at the normal rate. Hydroxylation of lysine residues on procollagen... 

B. Hydroxylation of lysine residues requires vitamin C and occurs after lysine has been incorporated into the polypeptide chain but before secretion from the cell. Hydroxylysine residues form cross links between collagen molecules, causing polymerization. 

The protein collagen is unusual in its widespread modification of proline to 4-hydroxyproline (also called hydroxyproline). The OH groups of hydroxyproline participate in stabilizing the structure. Hydroxylation of lysine residues in collagen also occurs but is much less frequent. It plays a different role, serving to form attachment sites for polysaccharides. 

Peptidyllysine, 2-oxoglularate oxygen 5-oxidoreduc-tase, or Lysine, 2-oxoglutarate dioxygenase, or Lysine hydroxylase (EC 1.14.11.4). It catalyses hydroxylation of lysine residues in procollagen, forming residues of... 

So far, the function of lysyl hydroxylation and glycosylation of Hyls is not clear. In some diseases such as 01, an overmodification of lysine residues occurs. It has been postulated that the triple helix formation is slower in these cases and therefore the unfolded chains are exposed for a longer time to the modifying enzymes. 

Figure 3 Mechanism of steroid-induced cataract according to the most prominent hypothesis. It involves first the formation of Schiff bases between the steroid C-20 ketone group and nucleophilic groups such as e-amino groups of lysine residues of proteins and then a Heyns rearrangement involving the adjacent C-21 hydroxyl group that results in stable amine-linked adducts.

The other major protein in the extracellular matrix is elastin, which is the main component of elastic fibers found in ligaments, large arteries, and lungs. After synthesis and partial hydroxylation of proline residues, a 72 kDa molecule of tropoelastin is secreted into the matrix. This protein is rich in nonpolar amino acids and contains repeating sequences, such as (Val-Pro-Gly-Val-Gly). These sections form an amorphous, random-coiled structure with frequent reverse turns. Other recurrent sequences are rich in alanine with paired lysine residues, e.g., -Ala-Ala-Ala-Ala-Lys-Ala-Ala-Lys-... 

Protein phosphorylation is a pervasive posttranslational modification in cells. It is reversible and can dramatically affect the activity of a modified protein. Protein phosphorylation is one of the most important mechanisms used for signal transduction by cells. In prokaryotic cells, the best-known reversible protein phosphorylations occur on histidine and aspartate in eukaryotes the best-known occur on the hydroxyl groups of serine, threonine, and tyrosine, although histidine can also be phosphorylated (Fig. 3.9). Other reversible modifications also occur, such as the acetylation of lysine residues in histone proteins. 

Figure 1.18 Reaction of proline, arginine, and lysine residues with hydroxyl radical results in oxidation of side-chain structures that form carbonyls. Both arginine and proline oxidation result in the same product.

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