Target type: molecularfunction
Catalysis of the reaction: A + 2-oxoglutarate + O2 = B + succinate + CO2. This is an oxidation-reduction (redox) reaction in which hydrogen or electrons are transferred from 2-oxoglutarate and one other donor, and one atom of oxygen is incorporated into each donor. [GOC:mah]
2-oxoglutarate-dependent dioxygenases (2-ODDs) are a diverse family of enzymes that catalyze a wide range of reactions involving the oxidation of a variety of substrates. These enzymes are characterized by their requirement for 2-oxoglutarate (α-ketoglutarate), molecular oxygen, and ferrous iron as cofactors. The catalytic cycle of 2-ODDs begins with the binding of 2-oxoglutarate and molecular oxygen to the active site. The ferrous iron then coordinates with the oxygen molecule, which is activated and cleaved to form a reactive oxygen species, typically a ferryl species. This reactive oxygen species is then used to oxidize the substrate, which is typically a carbon-hydrogen bond. The oxidation reaction results in the formation of a hydroxyl group on the substrate and the release of carbon dioxide from 2-oxoglutarate, which is converted to succinate. The oxidized substrate can then undergo further reactions, such as decarboxylation, ring opening, or rearrangement. 2-ODDs are involved in a wide range of cellular processes, including collagen biosynthesis, DNA repair, hormone synthesis, and the regulation of gene expression. They are also implicated in a number of diseases, such as cancer, neurodegenerative disorders, and cardiovascular disease. 2-ODDs are highly regulated enzymes, and their activity is often influenced by factors such as the availability of substrates, cofactors, and inhibitors. The regulation of 2-ODD activity is critical for maintaining cellular homeostasis and for preventing the development of disease.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Bifunctional peptidase and (3S)-lysyl hydroxylase JMJD7 | A bifunctional peptidase and (3S)-lysyl hydroxylase JMJD7 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P0C870] | Homo sapiens (human) |
| Histone lysine demethylase PHF8 | A histone lysine demethylase PHF8 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9UPP1] | Homo sapiens (human) |
| Transmembrane prolyl 4-hydroxylase | A transmembrane prolyl 4-hydroxylase that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9NXG6] | Homo sapiens (human) |
| Prolyl hydroxylase EGLN3 | A prolyl hydroxylase EGLN3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9H6Z9] | Homo sapiens (human) |
| Egl nine homolog 1 | An egl nine homolog 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9GZT9] | Homo sapiens (human) |
| Prolyl hydroxylase EGLN2 | A prolyl hydroxylase EGLN2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q96KS0] | Homo sapiens (human) |
| Lysine-specific demethylase 7A | A lysine-specific demethylase 7A that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q6ZMT4] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| alpha-ketoglutaric acid | 2-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 acid | fundamental metabolite |
| picolinic acid | picolinic 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 acid | human metabolite; MALDI matrix material |
| succinic acid | succinic acid : An alpha,omega-dicarboxylic acid resulting from the formal oxidation of each of the terminal methyl groups of butane to the corresponding carboxy group. It is an intermediate metabolite in the citric acid cycle. Succinic Acid: A water-soluble, colorless crystal with an acid taste that is used as a chemical intermediate, in medicine, the manufacture of lacquers, and to make perfume esters. It is also used in foods as a sequestrant, buffer, and a neutralizing agent. (Hawley's Condensed Chemical Dictionary, 12th ed, p1099; McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed, p1851) | alpha,omega-dicarboxylic acid; C4-dicarboxylic acid | anti-ulcer drug; fundamental metabolite; micronutrient; nutraceutical; radiation protective agent |
| isocitric acid | isocitric acid : A tricarboxylic acid that is propan-1-ol with a hydrogen at each of the 3 carbon positions replaced by a carboxy group. isocitric acid: RN given refers to unlabeled parent cpd | secondary alcohol; tricarboxylic acid | fundamental metabolite |
| 2,2'-dipyridyl | 2,2'-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. | bipyridine | chelator; ferroptosis inhibitor |
| amiodarone | amiodarone : A member of the class of 1-benzofurans that is 1-benzofuran substituted by a butyl group at position 2 and a 4-[2-(diethylamino)ethoxy]-3,5-diiodobenzoyl group at position 3. It is a cardiovascular drug used for the treatment of cardiac dysrhythmias. Amiodarone: An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance. | 1-benzofurans; aromatic ketone; organoiodine compound; tertiary amino compound | cardiovascular drug |
| fusaric acid | Fusaric 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 | |
| succinylacetone | 4,6-dioxoheptanoic acid : A dioxo monocarboxylic acid that is heptanoic acid in which oxo groups replace the hydrogens at positions 4 and 6. It is an abnormal metabolite of the tyrosine metabolic pathway and a marker for type 1 tyrosinaemia. succinylacetone: inhibitor of heme biosynthesis | beta-diketone; dioxo monocarboxylic acid | human metabolite |
| 2,5-pyridinedicarboxylic acid | 2,5-Pyridinedicarboxylic acid: RN given refers to parent cpd isocinchomeronic acid : A pyridinedicarboxylic acid carrying carboxy groups at positions 2 and 5. | pyridinedicarboxylic acid | |
| glycyrrhetinic acid | cyclic terpene ketone; hydroxy monocarboxylic acid; pentacyclic triterpenoid | immunomodulator; plant metabolite | |
| salicylurate | salicylurate : A monocarboxylic acid anion that is the conjugate base of salicyluric acid, obtained by deprotonation of the carboxy group; major species at pH 7.3. salicylurate: RN given refers to parent cpd salicyluric acid : An N-acylglycine in which the acyl group is specified as 2-hydroxybenzoyl. | N-acylglycine; secondary carboxamide | human xenobiotic metabolite; uremic toxin |
| 2,4-pyridinedicarboxylic acid | lutidinic acid : A pyridinedicarboxylic acid carrying carboxy groups at positions 2 and 4. | pyridinedicarboxylic acid | |
| oleanolic acid | hydroxy monocarboxylic acid; pentacyclic triterpenoid | plant metabolite | |
| daminozide | daminozide: induces tumors | straight-chain fatty acid | |
| ursolic acid | hydroxy monocarboxylic acid; pentacyclic triterpenoid | geroprotector; plant metabolite | |
| betulinic acid | hydroxy 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 eupatoria | dihydroxy monocarboxylic acid; pentacyclic triterpenoid | anti-inflammatory agent; antineoplastic agent; antioxidant; plant metabolite |
| fumaric acid | fumaric acid : A butenedioic acid in which the C=C double bond has E geometry. It is an intermediate metabolite in the citric acid cycle. fumaric acid: see also record for ferrous fumarate; use FUMARATES for general fumaric acid esters | butenedioic acid | food acidity regulator; fundamental metabolite; geroprotector |
| 5-carboxy-8-hydroxyquinoline | 5-carboxy-8-hydroxyquinoline: a JmjC histone demethylase inhibitor; structure in first source | quinolines | |
| oxalylglycine | N-oxalylglycine : An amino dicarboxylic acid that is iminodiacetic acid with an oxo substituent. It is used as an inhibitor of alpha-ketoglutarate dependent (EC 1.14.11.*) enzymes. oxalylglycine: structure given in first source | amino dicarboxylic acid; N-acylglycine | EC 1.14.11.* (oxidoreductase acting on paired donors, 2-oxoglutarate as one donor, incorporating 1 atom each of oxygen into both donors) inhibitor |
| vidofludimus | vidofludimus: a dihydroorotate dehydrogenase inhibitor; structure in first source | ||
| fg-4592 | roxadustat : 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 |
| jnj 42041935 | |||
| ascorbic acid | Ascorbic 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 |
| 2-[[[4-hydroxy-2-oxo-1-(phenylmethyl)-3-quinolinyl]-oxomethyl]amino]acetic acid | quinolines | ||
| 3-[[2-(2-pyridinyl)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-4-pyrimidinyl]amino]propanoic acid | organonitrogen heterocyclic compound | ||
| bay 85-3934 | |||
| gsk1278863 | daprodustat : A member of the class of barbiturates that is barbituric acid substituted by cyclohexyl groups at positions 1 and 3, and by a (carboxymethyl)aminocarbonyl group at position 5. It is an inhibitor of hypoxia-inducible factor prolyl hydroxylase developed by GlaxoSmithKline for the treatment of anaemia in patients with chronic kidney disease. GSK1278863: a HIF prolyl hydroxylase inhibitor |