What is the function of prolyl 4-hydroxylase within your own body?
What is the function of prolyl 4-hydroxylase within your own body?
Prolyl-4-hydroxylase (P4H) is a non-heme iron hydroxylase that regio- and stereospecifically hydroxylates proline residues in a peptide chain into R-4-hydroxyproline, which is essential for collagen cross-linking purposes in the human body.
Which subunit of prolyl 4-hydroxylase has catalytic activity?
α subunit
Enzyme structure Prolyl hydroxylase is a tetramer with 2 unique subunits. The α subunit is 59 kDa and is responsible for both peptide binding and for catalytic activity.
What does prolyl hydroxylase do?
The prolyl hydroxylase domain (PHD) enzymes regulate the stability of the hypoxia-inducible factor (HIF) in response to oxygen availability. During oxygen limitation, the inhibition of PHD permits the stabilization of HIF, allowing the cellular adaptation to hypoxia.
What is CP4H?
The enzyme collagen prolyl 4-hydroxylase (CP4H) is a non-heme Fe(II)- and α-ketoglutarate-dependent dioxygenase (FAKGD) that catalyzes the stereoselective hydroxylation of Cγ of (2S)-proline (Pro) residues in collagen strands. This uncoupled reaction inactivates the enzyme.
What is the other product found in collagen of this reaction catalyzed by prolyl hydroxylase?
Collagenous domains as substrates. The (Xaa–Yaa–Gly)n amino-acid sequence that is characteristic of collagen is found in other proteins as well. These sequences form triple helices, though the triple-helical domains are usually much shorter than those in collagen.
How does ascorbic acid vitamin C affect prolyl hydroxylase function?
2 Ascorbic acid (vitamin C) Ascorbic acid is an essential cofactor for the enzyme prolyl hydroxylase, and a deficiency of this vitamin results in accumulation of abnormal collagen.
What does prolyl hydroxylase do to collagen?
Collagen prolyl 4-hydroxylase (P4H) is an α2β2 tetrameric α-ketoglutarate (α-KG)-dependent dioxygenase that catalyzes 4-hydroxylation of proline to promote formation of the collagen triple helix, releasing succinate as a product3.
What is peptidyl prolyl hydroxylase?
Prolyl hydroxylase (proline,2-oxoglutarate dioxygenase, EC 1.14. 11.2) is a mixed-function oxygenase that hydroxylates peptidyl proline with the simultaneous and stoichiometric decarboxylation of alpha-ketoglutarate to succinate and CO2.
Where is prolyl hydroxylase found?
Hyp is also found in proteins with collagen-like domains, as well as elastin, conotoxins, and argonaute 2. A prolyl hydroxylase domain protein acts on the hypoxia inducible factor α, which plays a key role in sensing molecular oxygen, and could act on inhibitory κB kinase and RNA polymerase II.
What are the cofactors of hydroxylation of proline residues in collagen?
The hydroxylation occurs during protein synthesis and requires ascorbic acid (vitamin C) as a cofactor. Deficiency of vitamin C causes formation of defective collagen and scurvy.
What is a prolyl residue?
Prolyl isomerase (also known as peptidylprolyl isomerase or PPIase) is an enzyme (EC 5.2. 1.8) found in both prokaryotes and eukaryotes that interconverts the cis and trans isomers of peptide bonds with the amino acid proline.
What is meant by hydroxylation?
(i) most commonly, hydroxylation describes a chemical process that introduces a hydroxyl group (-OH) into an organic compound. (ii) the degree of hydroxylation refers to the number of OH groups in a molecule. The pattern of hydroxylation refers to the location of hydroxy groups on a molecule or material.
