Gene Targets > procollagen-proline 4-dioxygenase activity
Page last updated: 2024-10-24

procollagen-proline 4-dioxygenase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: procollagen L-proline + 2-oxoglutarate + O2 = procollagen trans-4-hydroxy-L-proline + succinate + CO2. [EC:1.14.11.2]

Procollagen-proline 4-dioxygenase activity catalyzes the hydroxylation of proline residues in the Y position of the repeating -Gly-X-Y- sequence of collagen precursor molecules. This hydroxylation is a crucial step in the biosynthesis of collagen, which is the main structural protein in connective tissues.

The enzyme requires molecular oxygen, ferrous iron, and ascorbate (vitamin C) as cofactors for its activity. It specifically hydroxylates proline residues in the Y position, which are typically located in the middle of the Gly-X-Y tripeptide repeat.

Hydroxylation of proline residues in collagen has several important consequences:

- It increases the stability of the collagen triple helix structure. Hydroxylated proline residues form hydrogen bonds with other amino acid residues, which stabilize the helix.
- It promotes the assembly of collagen fibrils. Hydroxylated proline residues are involved in interactions with other collagen molecules, which are necessary for the formation of fibrils.
- It affects the mechanical properties of collagen. Hydroxylated proline residues contribute to the tensile strength and elasticity of collagen.

Deficiency in procollagen-proline 4-dioxygenase activity can lead to collagen disorders, such as osteogenesis imperfecta, which is characterized by fragile bones.
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Proteins (4)

ProteinDefinitionTaxonomy
Prolyl 4-hydroxylase subunit alpha-1[no definition available]Gallus gallus (chicken)
Transmembrane prolyl 4-hydroxylaseA transmembrane prolyl 4-hydroxylase that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9NXG6]Homo sapiens (human)
Prolyl 4-hydroxylase subunit alpha-1A prolyl 4-hydroxylase subunit alpha-1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P13674]Homo sapiens (human)
Protein disulfide-isomeraseA protein disulfide-isomerase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P07237]Homo sapiens (human)

Compounds (34)

CompoundDefinitionClassesRoles
2,3-dihydroxybenzoic acid2,3-dihydroxybenzoic acid : A dihydroxybenzoic acid that is benzoic acid substituted by hydroxy groups at positions 2 and 3. It occurs naturally in Phyllanthus acidus and in the aquatic fern Salvinia molesta.

2,3-dihydroxybenzoic acid: RN given refers to parent cpd

dihydroxybenzoic acid : Any member of the class of hydroxybenzoic acids carrying two phenolic hydroxy groups on the benzene ring and its derivatives.		dihydroxybenzoic acidhuman xenobiotic metabolite;
plant metabolite
alpha-ketoglutaric acid2-oxoglutaric acid : An oxo dicarboxylic acid that consists of glutaric acid bearing an oxo substituent at position 2. It is an intermediate metabolite in Krebs cycle.oxo dicarboxylic acidfundamental metabolite
protocatechuic acid3,4-dihydroxybenzoic acid : A dihydroxybenzoic acid in which the hydroxy groups are located at positions 3 and 4.

protocatechuic acid: RN given refers to parent cpd; structure		catechols;
dihydroxybenzoic acid		antineoplastic agent;
EC 1.1.1.25 (shikimate dehydrogenase) inhibitor;
EC 1.14.11.2 (procollagen-proline dioxygenase) inhibitor;
human xenobiotic metabolite;
plant metabolite
4-hydroxybenzoic acid4-hydroxybenzoic acid : A monohydroxybenzoic acid that is benzoic acid carrying a hydroxy substituent at C-4 of the benzene ring.monohydroxybenzoic acidalgal metabolite;
plant metabolite
catecholcatecholsallelochemical;
genotoxin;
plant metabolite
salicylic acidScalp: The outer covering of the calvaria. It is composed of several layers: SKIN; subcutaneous connective tissue; the occipitofrontal muscle which includes the tendinous galea aponeurotica; loose connective tissue; and the pericranium (the PERIOSTEUM of the SKULL).monohydroxybenzoic acidalgal metabolite;
antifungal agent;
antiinfective agent;
EC 1.11.1.11 (L-ascorbate peroxidase) inhibitor;
keratolytic drug;
plant hormone;
plant metabolite
gallic acidgallate : A trihydroxybenzoate that is the conjugate base of gallic acid.trihydroxybenzoic acidantineoplastic agent;
antioxidant;
apoptosis inducer;
astringent;
cyclooxygenase 2 inhibitor;
EC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor;
geroprotector;
human xenobiotic metabolite;
plant metabolite
3,4-dihydroxyphenylacetic acid(3,4-dihydroxyphenyl)acetic acid : A dihydroxyphenylacetic acid having the two hydroxy substituents located at the 3- and 4-positions. It is a metabolite of dopamine.

3,4-Dihydroxyphenylacetic Acid: A deaminated metabolite of LEVODOPA.

dihydroxyphenylacetic acid : A dihydroxy monocarboxylic acid consisting of phenylacetic acid having two phenolic hydroxy substituents.		catechols;
dihydroxyphenylacetic acid		human metabolite
glucono-1,4-lactonegamma-lactone
hydroquinonebenzenediol;
hydroquinones		antioxidant;
carcinogenic agent;
cofactor;
Escherichia coli metabolite;
human xenobiotic metabolite;
mouse metabolite;
skin lightening agent
phenylacetic acidphenylacetic acid : A monocarboxylic acid that is toluene in which one of the hydrogens of the methyl group has been replaced by a carboxy group.benzenes;
monocarboxylic acid;
phenylacetic acids		allergen;
Aspergillus metabolite;
auxin;
EC 6.4.1.1 (pyruvate carboxylase) inhibitor;
Escherichia coli metabolite;
human metabolite;
plant growth retardant;
plant metabolite;
Saccharomyces cerevisiae metabolite;
toxin
picolinic acidpicolinic acid : A pyridinemonocarboxylic acid in which the carboxy group is located at position 2. It is an intermediate in the metabolism of tryptophan.

picolinic acid: iron-chelating agent that inhibits DNA synthesis; may interfere with iron-dependent production of stable free organic radical which is essential for ribonucleotide reductase formation of deoxyribonucleotides; RN given refers to parent cpd; structure in Merck Index, 9th ed, #7206		pyridinemonocarboxylic acidhuman metabolite;
MALDI matrix material
pyrogallolbenzenetriol : A triol in which three hydroxy groups are substituted onto a benzene ring.benzenetriol;
phenolic donor		plant metabolite
mandelic acidSAMMA: mandelic acid condensation polymer2-hydroxy monocarboxylic acid;
benzenes		antibacterial agent;
human xenobiotic metabolite
2,2'-dipyridyl2,2'-bipyridine : A bipyridine in which the two pyridine moieties are linked by a bond between positions C-2 and C-2'.

2,2'-Dipyridyl: A reagent used for the determination of iron.		bipyridinechelator;
ferroptosis inhibitor
beta-resorcylic acidbeta-resorcylic acid: RN given refers to parent cpd; structure
fusaric acidFusaric Acid: A picolinic acid derivative isolated from various Fusarium species. It has been proposed for a variety of therapeutic applications but is primarily used as a research tool. Its mechanisms of action are poorly understood. It probably inhibits DOPAMINE BETA-HYDROXYLASE, the enzyme that converts dopamine to norepinephrine. It may also have other actions, including the inhibition of cell proliferation and DNA synthesis.aromatic carboxylic acid;
pyridines
2,5-dihydroxybenzoic acid2,5-dihydroxybenzoic acid : A dihydroxybenzoic acid having the two hydroxy groups at the 2- and 5-positions.

2,5-dihydroxybenzoic acid: RN given refers to parent cpd; a oxidative product of saligenin		dihydroxybenzoic acidEC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor;
fungal metabolite;
human metabolite;
MALDI matrix material;
mouse metabolite
resorcinolresorcinol : A benzenediol that is benzene dihydroxylated at positions 1 and 3.

resorcinol: RN given refers to parent cpd; structure in Merck Index, 9th ed, #7951		benzenediol;
phenolic donor;
resorcinols		erythropoietin inhibitor;
sensitiser
3-hydroxybenzoic acid3-hydroxybenzoic acid : A monohydroxybenzoic acid that is benzoic acid substituted by a hydroxy group at position 3. It has been isolated from Taxus baccata. It is used as an intermediate in the synthesis of plasticisers, resins, pharmaceuticals, etc.

3-hydroxybenzoic acid: RN given refers to parent cpd		monohydroxybenzoic acidbacterial metabolite;
plant metabolite
alpha-resorcylic acid3,5-dihydroxybenzoic acid : A dihydroxybenzoic acid in which the hydroxy groups are located at positions 3 and 5.

alpha-resorcylic acid: RN given refers to parent cpd		dihydroxybenzoic acid;
resorcinols		metabolite
2,5-pyridinedicarboxylic acid2,5-Pyridinedicarboxylic acid: RN given refers to parent cpd

isocinchomeronic acid : A pyridinedicarboxylic acid carrying carboxy groups at positions 2 and 5.		pyridinedicarboxylic acid
gamma-resorcylic aciddihydroxybenzoic acidmetabolite
glycyrrhetinic acidcyclic terpene ketone;
hydroxy monocarboxylic acid;
pentacyclic triterpenoid		immunomodulator;
plant metabolite
oleanolic acidhydroxy monocarboxylic acid;
pentacyclic triterpenoid		plant metabolite
ursolic acidhydroxy monocarboxylic acid;
pentacyclic triterpenoid		geroprotector;
plant metabolite
betulinic acidhydroxy monocarboxylic acid;
pentacyclic triterpenoid		anti-HIV agent;
anti-inflammatory agent;
antimalarial;
antineoplastic agent;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
plant metabolite
maslinic acid(2Alpha,3beta)-2,3-dihydroxyolean-12-en-28-oic acid: from Luehea divaricata and Agrimonia eupatoriadihydroxy monocarboxylic acid;
pentacyclic triterpenoid		anti-inflammatory agent;
antineoplastic agent;
antioxidant;
plant metabolite
3,4-dihydroxymandelic acid3,4-dihydroxymandelic acid : A catechol that is the 3,4-dihydroxy derivative of mandelic acid; a metabolite of L-dopa.

3,4-dihydroxymandelic acid: metabolite of L-dopa; RN given refers to parent cpd without isomeric designation		2-hydroxy monocarboxylic acid;
catechols		antioxidant;
drug metabolite;
human metabolite;
mouse metabolite
3,4-dihydroxyphenylpropionic acid3-(3,4-dihydroxyphenyl)propanoic acid : A monocarboxylic acid that is 3-phenylpropionic acid substituted by hydroxy groups at positions 3 and 4. Also known as dihydrocaffeic acid, it is a metabolite of caffeic acid and exhibits antioxidant activity.

3,4-dihydroxyphenylpropionic acid: metabolite of caffeic acid; RN given refers to parent cpd; structure		(dihydroxyphenyl)propanoic acidantioxidant;
human xenobiotic metabolite
isoliquiritigeninchalconesantineoplastic agent;
biological pigment;
EC 1.14.18.1 (tyrosinase) inhibitor;
GABA modulator;
geroprotector;
metabolite;
NMDA receptor antagonist
caffeic acidtrans-caffeic acid : The trans-isomer of caffeic acid.caffeic acidgeroprotector;
mouse metabolite
galangin5,7-dihydroxyflavonol: antimicrobial from the twigs of Populus nigra x Populus deltoides; structure in first source

galangin : A 7-hydroxyflavonol with additional hydroxy groups at positions 3 and 5 respectively; a growth inhibitor of breast tumor cells.		7-hydroxyflavonol;
trihydroxyflavone		antimicrobial agent;
EC 3.1.1.3 (triacylglycerol lipase) inhibitor;
plant metabolite
ascorbic acidAscorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant.

L-ascorbate : The L-enantiomer of ascorbate and conjugate base of L-ascorbic acid, arising from selective deprotonation of the 3-hydroxy group. Required for a range of essential metabolic reactions in all animals and plants.

L-ascorbic acid : The L-enantiomer of ascorbic acid and conjugate acid of L-ascorbate.

vitamin C : Any member of a group of vitamers that belong to the chemical structural class called butenolides that exhibit biological activity against vitamin C deficiency in animals. The vitamers include L-ascorbic acid and its salt, ionized and oxidized forms.		ascorbic acid;
vitamin C		coenzyme;
cofactor;
flour treatment agent;
food antioxidant;
food colour retention agent;
geroprotector;
plant metabolite;
skin lightening agent
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