Principles of Protein Structure - H. Schulz 1982

Covalent Protein Structure
Enzyme-Controlled Modifications of Side Chains
Cross-Links Based on Modified Lys Residues

The formation of ε-(γ-glutamyl)Lysine bonds*, for example, is essential in the enzymatic coagulation of rodent semen [158] or in Blood clotting during the stabilization of fragile fibrin aggregates [159]. Cross-links between polypeptide chains in Elastin (Fig. 4.7) and Collagen (Fig. 4.4) are likewise formed by the side chains of lysine residues. In elastin, a rubber-like protein, cross-links appear to be crucial for ensuring that elastin fibers return to their initial state after stretching. Cross-links between collagen molecules contribute to the Stability of the triple helix; this Structure is thermolabile and melts into gelatin at approximately 40°C [125, 127]. Thus, intra- and intermolecular cross-links between polypeptide chains in collagen prevent this most abundant protein in The Human Body from converting into an amorphous gelatin at temperatures approaching 40°C during a fever. In all the aforementioned Proteins, covalent cross-links are essential for stabilization rather than for the initial formation of protein structures—a feature shared by certain Disulfide bridges as well (Sec. 4.2).

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Fig. 4.7. Desmosine, formed by the joining of four lysine side chains; found in elastin.

* According to the nomenclature of Fig. 1.1, ξ-(δ-glutamyl)lysine.

Table 4.3 Examples of side chain modifications

Modification

Modified side chains

A specific, not necessarily typical example

Functional aspect

Adenylation [168]

Tyr

Glutamine Synthetase

Adenylation of a single Tyr per subunit converts the enzyme from a form whose biosynthetic activity depends on Mg2+ (optimal pH 7.6) to a form dependent on Mn2+ (optimal pH 6.5)

ADP-ribosylation [169]

Lys or Arg

Elongation factor EF2

This modification is catalyzed by diphtheria toxin [165], inhibits Biosynthesis, and leads to Cell death

Carboxylation [170, 171]

Glu

Prothrombin and other blood-clotting factors (VII, IX, X)

Modified glutamic acid residues are required for normal Ca2+ binding by prothrombin, i.e., for the Ca2+-mediated attachment of prothrombin to phospholipid surfaces

Glycosylation [172, 173]

Asn, Thr, Ser

Ceruloplasmin

Loss of the terminal carbohydrate unit in the side chains of serum Glycoproteins serves as a signal for the uptake and degradation of these proteins in the Liver

Hydroxylation [125, 127]

Pro, Lys

Collagen

Impaired hydroxylation prevents collagen maturation; this is the Molecular Basis of scurvy

Methylation [174]

Asp, Gln, His, Lys, Arg

ε-N-Methyllysine in protein side chains

Despite the widespread occurrence of these reactions, there are no examples proving a direct correlation between protein methylation and a specific function

Phosphorylation [175]

Ser, Thr

Phosphorylase

Inactive phosphorylase b is converted into active phosphorylase a by the phosphorylation of a specific Serine residue in each subunit


Last update: 06/08/2026

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