peptidyl-proline hydroxylation

Definition

Target type: biologicalprocess

The hydroxylation of peptidyl-proline to form peptidyl-hydroxyproline. [GOC:mah]

Peptidyl-proline hydroxylation is a crucial post-translational modification that plays a pivotal role in protein folding, stability, and function. This process involves the enzymatic addition of a hydroxyl group to the proline residue within a polypeptide chain. The enzyme responsible for this modification is prolyl 4-hydroxylase (P4H), which requires molecular oxygen, α-ketoglutarate, and ascorbate (vitamin C) as cofactors.

The reaction occurs in two distinct steps. First, P4H binds to the proline residue within a specific sequence motif, typically a proline residue followed by a glycine residue (Pro-Gly). This binding event is crucial for the enzyme's specificity and ensures that only specific proline residues are hydroxylated. Second, P4H utilizes molecular oxygen and α-ketoglutarate to catalyze the hydroxylation of the proline residue, forming 4-hydroxyproline. This reaction results in the introduction of a hydroxyl group onto the γ-carbon of the proline ring, creating a new chiral center.

The hydroxylation of proline residues has profound implications for protein structure and function. 4-hydroxyproline residues are more hydrophilic than proline residues, which can significantly alter the local conformation of the protein. In particular, the presence of 4-hydroxyproline residues promotes the formation of tight turns and bends in the polypeptide chain, which are essential for the stability and proper folding of collagen and other structural proteins.

Furthermore, peptidyl-proline hydroxylation can influence protein-protein interactions and signaling pathways. For instance, hydroxylation of specific proline residues within the hypoxia-inducible factor (HIF) pathway regulates the stability and activity of HIF proteins, thereby influencing cellular responses to low oxygen levels.

In summary, peptidyl-proline hydroxylation is a fundamental post-translational modification that plays a vital role in protein folding, stability, and function. This process involves the enzymatic addition of a hydroxyl group to specific proline residues within a polypeptide chain, significantly impacting protein structure, protein-protein interactions, and cellular signaling pathways.'
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Proteins (2)

Compounds (2)