peptidyl-lysine hydroxylation

Definition

Target type: biologicalprocess

The hydroxylation of peptidyl-lysine to form peptidyl-hydroxylysine. [GOC:ai]

Peptidyl-lysine hydroxylation is a post-translational modification that involves the enzymatic addition of a hydroxyl group to the ε-amino group of lysine residues within a protein. This process is catalyzed by a family of enzymes known as lysyl hydroxylases, which require molecular oxygen, Fe(II), and α-ketoglutarate as cofactors. The reaction proceeds in two steps:

1. **Oxygen Activation and α-Ketoglutarate Decarboxylation:** The lysyl hydroxylase binds to both oxygen and α-ketoglutarate. Oxygen is activated by the enzyme's iron center, while α-ketoglutarate undergoes decarboxylation, releasing carbon dioxide. This process generates a highly reactive intermediate called a ferryl-oxo species.

2. **Hydroxylation of Lysine:** The ferryl-oxo species then attacks the ε-amino group of the lysine residue, leading to the formation of a hydroxylated lysine residue and the regeneration of the enzyme's iron center.

The hydroxylation of lysine residues can significantly alter the properties and functions of proteins. Some of the key effects include:

* **Increased Protein Stability:** Hydroxylation can increase the stability of the protein by promoting the formation of hydrogen bonds and other interactions.
* **Enhanced Protein-Protein Interactions:** Hydroxylated lysines can serve as binding sites for other proteins, facilitating protein-protein interactions.
* **Altered Protein Conformation:** The addition of a hydroxyl group can alter the local conformation of the protein, influencing its overall structure and function.

Peptidyl-lysine hydroxylation plays a crucial role in various biological processes, including:

* **Collagen Synthesis:** Hydroxylation of lysine residues in collagen is essential for the formation of stable triple helix structures, which provide strength and integrity to connective tissues.
* **Elastin Synthesis:** Hydroxylation of lysine residues in elastin contributes to the elasticity and resilience of tissues like blood vessels and skin.
* **Hypoxia Signaling:** Hydroxylation of specific lysine residues in hypoxia-inducible factor (HIF) regulates its stability and activity, influencing cellular responses to low oxygen conditions.
* **Immune Response:** Hydroxylation of lysine residues in immune proteins like antibodies can modulate their binding affinities and effector functions.

Overall, peptidyl-lysine hydroxylation is a critical post-translational modification that plays a diverse role in cellular function and human health. It influences protein structure, stability, interactions, and signaling pathways, impacting a wide range of biological processes.'
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Proteins (1)

Compounds (1)