Prolyl 3-hydroxylase 1 (P3H1)

Prolyl 3-hydroxylase 1 (P3H1) is an **enzyme** of the 2-oxoglutarate and Fe(II)-dependent oxygenase superfamily, responsible for the post-translational hydroxylation of specific proline residues (notably Pro986 in the α1 chain of type I collagen)[1][2]. P3H1 typically functions as part of an endoplasmic reticulum-associated ternary complex with CRTAP and PPIB (known as the PCP complex)[2][3]. This multi-protein assembly acts both as a **hydroxylation enzyme** and a **molecular chaperone**, ensuring proper folding and assembly of collagen triple helices[1][2]. Deficiency or mutations in any component of this complex—especially LEPRE1 (the gene encoding P3H1)—cause autosomal recessive forms of osteogenesis imperfecta (OI), a disorder marked by bone fragility and other connective tissue issues[1][2]. P3H1 is highly specific in substrate recognition, and the absence of its enzymatic function results in a lack of 3-hydroxylation at key residues, leading to abnormal collagen[1][2]. At the structural level, P3H1 contains a highly conserved “jelly roll” motif crucial for Fe(II) and 2-oxoglutarate binding, the cofactors required for its oxygenase activity[2][3]. No drugs are currently approved that directly target P3H1, but its clear involvement in severe genetic disease makes it of significant interest as a biochemical and diagnostic target[1][2][3].

Other names

Prolyl 3-hydroxylase 1P3H1GROS1LEPRE1LEPRECANLeprecan-1Growth suppressor 1Leucine- and proline-enriched proteoglycan 1Prococollagen-proline 3-dioxygenaseOI8MGC117314PSEC0109

(For any future drugs) Inhibition or modulation of enzymatic hydroxylation of proline in collagen by affecting P3H1 activity