peptidyl-lysine oxidation

Definition

Target type: biologicalprocess

The oxidation of the terminal amino-methylene groups of peptidyl-L-lysine or peptidyl-5-hydroxy-L-lysine to aldehyde groups to form allysine or hydroxyallysine residues, respectively; these are intermediates in the formation of covalent cross-links between adjacent polypeptide chains in proteins such as collagens. [ISBN:0198547684, RESID:AA0121]

Peptidyl-lysine oxidation is a post-translational modification (PTM) that involves the addition of an oxygen atom to the side chain of lysine residues in proteins. This process can occur on both free lysine residues and those within specific protein motifs. The oxidation of lysine residues can lead to a variety of functional changes in proteins, including changes in their structure, stability, and activity.

One of the most common forms of peptidyl-lysine oxidation is the formation of hydroxylysine. This modification is catalyzed by lysyl hydroxylases, a family of enzymes that utilize molecular oxygen and α-ketoglutarate as cofactors. Hydroxylysine residues are commonly found in collagen, where they play a role in the formation of strong intermolecular cross-links.

Another important form of peptidyl-lysine oxidation is the formation of Nε-(carboxymethyl)lysine (CML). This modification is formed through the reaction of lysine residues with glyoxal, a reactive dicarbonyl species. Glyoxal is a byproduct of glucose metabolism and can accumulate in tissues under conditions of oxidative stress. CML has been implicated in a variety of age-related diseases, including diabetes and Alzheimer's disease.

Peptidyl-lysine oxidation can also occur through the formation of advanced glycation end products (AGEs). AGEs are complex heterogeneous structures formed through the non-enzymatic glycation of proteins by sugars. The reaction of lysine residues with sugars can lead to the formation of a variety of AGE structures, including Nε-carboxymethyllysine (CML), Nε-(carboxyethyl)lysine (CEL), and pyrraline.

Peptidyl-lysine oxidation has been implicated in a wide range of biological processes, including:

* **Protein folding and stability:** Oxidation of lysine residues can alter the conformation of proteins, leading to changes in their stability and activity.
* **Protein-protein interactions:** Oxidation of lysine residues can affect the ability of proteins to interact with other proteins.
* **Cellular signaling:** Oxidation of lysine residues can alter the activity of signaling proteins.
* **Cellular stress response:** Peptidyl-lysine oxidation can be a marker of cellular stress and can trigger the activation of stress response pathways.

The biological significance of peptidyl-lysine oxidation depends on the specific lysine residue that is modified, the type of modification, and the cellular context. Understanding the role of peptidyl-lysine oxidation in different biological processes is essential for developing novel therapies for a variety of diseases.'
"

Proteins (5)

Compounds (15)