Page last updated: 2024-10-24

peptidyl-proline 3-dioxygenase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: peptidyl L-proline + 2-oxoglutarate + O2 = peptidyl trans-3-hydroxy-L-proline + succinate + CO2. [GOC:mah]

Peptidyl-proline 3-dioxygenase activity refers to the enzymatic ability to catalyze the hydroxylation of proline residues within peptides. This process involves the incorporation of molecular oxygen into the proline ring, specifically at the C3 position, forming a 3-hydroxyproline residue. This reaction is essential for various biological processes, including the formation of collagen, a major structural protein in connective tissues.

The enzyme responsible for this activity, known as prolyl 3-hydroxylase, requires a specific substrate containing a proline residue in a particular structural context. This context is typically dictated by the flanking amino acid residues and the overall conformation of the peptide.

The mechanism of the reaction involves the following steps:
1. Binding of the peptide substrate to the enzyme's active site.
2. Activation of molecular oxygen by the enzyme, typically facilitated by a metal cofactor such as iron.
3. Hydroxylation of the proline residue at the C3 position, resulting in the formation of 3-hydroxyproline.
4. Release of the hydroxylated peptide product from the enzyme.

The hydroxylation of proline by peptidyl-proline 3-dioxygenase activity plays a crucial role in the stability and function of collagen. The 3-hydroxyproline residues contribute to the rigidity and strength of the collagen fibrils by forming hydrogen bonds with other amino acid residues within the collagen molecule. Additionally, the 3-hydroxyproline residues can influence the folding and assembly of collagen fibrils, affecting their overall structure and properties.

In summary, peptidyl-proline 3-dioxygenase activity is a critical enzymatic process that contributes to the biosynthesis and integrity of collagen. This activity ensures the proper formation and function of connective tissues, which are essential for various physiological processes in the body.'
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Proteins (2)

ProteinDefinitionTaxonomy
Prolyl 3-hydroxylase OGFOD1A prolyl 3-hydroxylase OGFOD1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8N543]Homo sapiens (human)
Prolyl 3-hydroxylase OGFOD1A prolyl 3-hydroxylase OGFOD1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8N543]Homo sapiens (human)

Compounds (2)

CompoundDefinitionClassesRoles
fg-4592roxadustat : An N-acylglycine resulting from the formal condensation of the amino group of glycine with the carboxy group of 4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carboxylic acid. It is an inhibitor of hypoxia inducible factor prolyl hydroxylase (HIF-PH).

roxadustat: structure in first source
aromatic ether;
isoquinolines;
N-acylglycine
EC 1.14.11.2 (procollagen-proline dioxygenase) inhibitor;
EC 1.14.11.29 (hypoxia-inducible factor-proline dioxygenase) inhibitor
bay 85-3934