Collagen prosthetic groups

Lysine tyrosylquinone (LTQ) (Figure 3) is the protein-derived cofactor of mammalian lysyl oxidase, an important enzyme in the metabolism of connective tissue. Lysyl oxidase catalyzes the posttranslational modification of elastin and collagen. It oxidizes selected peptidyl lysine residues to peptidyl a-aminoadipic -semialdehyde residues. This initiates formation of the covalent cross-linkages that insolubilize these extracellular proteins. This enzyme also contains copper as a second prosthetic group. 

It is known that superoxide reacts very slowly with all amino-acids since all rate constants are below 100 mol l 1 s (89). Hence its reactivity with proteins without prosthetic group is low (89). One exception seems to be collagen, in which proline residues are oxidized into hydroxyproline (90). On the other hand, superoxide reacts efficiently with free radicals such as tryptophanyl radical (91). Reaction is fast with metalloproteins. It proceeds mostly by oxidizing or reducing the metal center. Some characteristics and rate constants of reactions with metalloproteins are given in table 7. It is obvious that products are often unknown and that the mechanism is sometimes unclear. It seems that there is no reaction with transferrin (92) and horseradish and lacto-peroxidase compounds II (93). The reason is unknown. 

Fig. 7. The disaccharide prosthetic group of the collagens and basement membranes.

Covalent modifications of proteins serve many purposes (1-4). Some are structural and affect the three dimensional structure of proteins, such as disulfide bonds or cross linking of collagen chains via allysine side chains. There are a many different modifications that allow for the attachment of a variety of nonpeptide prosthetic groups to the protein. The attachment of the heme group to cysteine in c type cytochromes and that of biotin or pyridoxal phosphate to lysine are but a few examples. Some processes, such as cysteine isoprenylation or N myristoylation, allow proteins to become tightly associated with membranes. In other situations, a protein may be regulated by a reversible reaction, such as phosphorylation. The best know examples of this are serine, threonine, and tyrosine phosphate esters. In many other cases, the function of a particular modification is less evident. 

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