Allysine residues

The strength and rigidity of a collagen fiber is imparted by covalent cross-links both between and within the tropocollagen molecules. As there are few, if any, Cys residues in the final mature collagen, these covalent cross-links are not disulfide bonds as commonly found in proteins, but rather are unique cross-links formed between Lys and its aldehyde derivative allysine. Allysine residues are formed from Lys by the action of the monooxygenase lysyl oxidase... 

Fig. 5). This copper-containing enzyme requires the coenzyme pyridoxal phosphate, derived from vitamin B6 (see Topic M2), for activity. The aldehyde group on allysine then reacts spontaneously with either the side-chain amino group of Lys or with other allysine residues on other polypeptide chains to form covalent interchain bonds. 

The free carbonyl residue can further condense with a histidyl group of another polypeptide chain to give a more complex cross-link. Schiff base formation, illustrated in Figure 8.4, involves an allysine residue at either the C- or N-terminal telopeptide and an uncharged lysine or hydroxylysine residue of another properly juxtaposed tropocollagen molecule. Such bonds are therefore intermolecular. Several other types of covalent cross-links are possible in collagens. They almost always involve lysine, allysine, hydroxylysine, hydroxyal-lysine, or histidine. 

Lysine residue Allysine residue Schiff base... 

Figure 8.4 Formation of an intermolecular cross-link in collagen. This type of cross-link involves an allysine residue of a telopeptide of one tropocollagen molecule and an amino group of a lysine residue located on the helical portion of another tropocollagen molecule.

Currently, there are at least two views related to the mechanism by which the desmosines are formed (19). These include the direct reaction of the so-called allysine aldol (cf. Figure 4) with dehydrolysinonorleucine to form desmosines, or alternatively, the reaction of dehydromerodesmosine with an allysine residue. 

The second mechanism would result from the stepwise addition of two allysines and lysine to form dehydromerodesmosine (via Michael additions) and then condensation with a fourth allysine residue. The major problem in resolving these points is the difficulty of sequencing around intra- and intermolecular crosslinks in a manner to provide definitive information. 

Formation of desmosine and isodesmosine covalent cross-links in elastin. Three allysine residues (Ra, R3, and R4) and one lysyl residue (R ) condense to give a desmosine cross-link. The allysine residues ( -aldehydes) are derived from the oxidative deamination of lysyl residues. The isodesmosine cross-link is formed similarly, except that it contains a substitution at position 2 rather than at position 4, along with substitutions at 1,3, and 5 on the pyridinium ring. 

Allysine then reacts with other side chain aldehyde or amino groups to form cross-linkages. For example, two allysine residues react to form an aldol cross-linked product ... 

The side chains of lysine residues also may be oxidized to form the aldehyde, allysine. These aldehyde residues produce covalent cross-links between collagen molecules (Fig. 49.4). An allysine residue on one collagen molecule reacts with the amino group of a lysine residue on another molecule, forming a covalent Schiff base that is converted to more stable covalent cross-links. Aldol condensation also may occur between two allysine residues, which forms the structure lysinonorleucine. 

Fig. 49.4. Formation of cross-links in collagen. A. Lysine residues are oxidized to allysine (an aldehyde). Allysine may react with an unmodified lysine residue to form a Schiff base (B), or two allysine residues may undergo an aldol condensation (C).

Allysine residue (L-a-aminoadipic semi aldehyde resid ue)... 

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