Collagen prolyl 4-hydroxylase (C-P4H) (C-P4H)

Collagen prolyl 4-hydroxylase (C-P4H) is a critical enzyme located in the lumen of the endoplasmic reticulum, responsible for the post-translational modification of collagen (Myllyharju, 2003; UniProt P13674). It catalyzes the hydroxylation of proline residues to 4-hydroxyproline, a modification essential for the thermal stability and structural integrity of the collagen triple helix (Gorres & Raines, 2010; PubMed 20092313). The enzyme typically exists as an alpha2-beta2 tetramer, where the alpha subunit provides the catalytic activity and the beta subunit (Protein Disulfide Isomerase) maintains the enzyme in a soluble, active conformation (Myllyharju, 2008; PMC2517483). In pathological states such as liver cirrhosis, pulmonary fibrosis, and various cancers, C-P4H is often upregulated, leading to excessive collagen deposition or a stiffened tumor microenvironment that promotes metastasis (Rappu et al., 2019; PubMed 31163359). Consequently, C-P4H is a significant therapeutic target for anti-fibrotic and anti-cancer drug development (Granchi et al., 2019; PubMed 31009205). Pharmacological inhibition usually involves small molecules that compete with the 2-oxoglutarate cofactor or the iron atom required for catalysis, effectively preventing the secretion of functional collagen (Vasta & Raines, 2018; PubMed 29474057).

Other names

Procollagen-proline 4-dioxygenaseProlyl 4-hydroxylaseP4HP4HAP4HBP4HA1P4HA2P4HA3

Inhibition of the catalytic alpha subunit prevents the hydroxylation of proline residues in procollagen chains, which destabilizes the collagen triple helix and leads to its intracellular degradation, thereby reducing extracellular matrix deposition (Myllyharju, 2003; PubMed 14505264).