Hydroxylysine cross-linking reaction

Collagen cross-links. Besides amide bonds between amino acids in the same a chain, bonds between amino acid side chains of different a chains can form "cross-links". These bonds originate from enzymatically-oxidized side chains of lysine and hydroxylysine residues. The oxidized residues react with other lysine and hydroxylysine residues, forming difunctional products. Reactions of such products with oxidized lysine or hydroxylysine yield trifunctional cross-links (Reiser et al., 1992). 

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. 

All the fibril-forming collagen t) es (t) e I, II, III, V, XI, XXIV, and XXVII collagens) are cross-linked through a mechanism based on the reactions of aldehydes derived from some lysine (or hydroxylysine) side chains. Histidine might also participate in the formation of a trivalent cross-link by reacting with an aldimine bond formed between a lysine aldehyde and hydroxylysine residue. 

Figure 5 Enzymatic cross-linking of collagen. Reaction of telopeptide lysine-aldehyde with triple-helical hydroxylysine to form the divalent aldimine cross-link A-HLNL. This cross-link reacts with triple-helical histidine to form the mature cross-link HHL.

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