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2-oxoglutarate (2OG)-dependent Dioxygenases
Alpha-ketoglutarate-dependent hydroxylases are a major class of non-heme iron proteins that catalyse a wide range of reactions. These reactions include hydroxylation reactions, demethylations, ring expansions, ring closures, and desaturations. Functionally, the αKG-dependent hydroxylases are comparable to cytochrome P450 enzymes. Both use O2 and reducing equivalents as cosubstrates and both generate water. Biological function αKG-dependent hydroxylases have diverse roles. In microorganisms such as bacteria, αKG-dependent dioxygenases are involved in many biosynthetic and metabolic pathways; for example, in ''E. coli'', the AlkB enzyme is associated with the repair of damaged DNA. In plants, αKG-dependent dioxygenases are involved in diverse reactions in plant metabolism. These include flavonoid biosynthesis, and ethylene biosyntheses. In mammals and humans, αKG-dependent dioxygenase have functional roles in biosyntheses (e.g. collagen biosynthesis and L-carnitine biosynthes ...
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Non-heme Iron Protein
In biochemistry, non-heme iron proteins describe families of enzymes that utilize iron at the active site but lack heme cofactors. Iron-sulfur proteins, including those that are enzymes, are not included in this definition. Some of non-heme iron proteins contain one Fe at their active sites, others have pairs of Fe centers: *Many mono-Fe proteins are alpha-ketoglutarate-dependent hydroxylases. Major examples are the lipoxygenases, isopenicillin N synthase, protocatechuate 3,4-dioxygenase, deacetoxycephalosporin-C synthase, and aromatic amino acid hydroxylases. *Major diiron enzymes include hemerythrin, some ribonucleotide reductases, some methane monooxygenases, purple acid phosphatases, and ferritin Ferritin is a universal intracellular protein that stores iron and releases it in a controlled fashion. The protein is produced by almost all living organisms, including archaea, bacteria, algae, higher plants, and animals. It is the primary ' ....{{cite journal , doi=10 ...
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Cysteine Dioxygenase
Cysteine dioxygenase (CDO) is a non-heme iron enzyme that catalyzes the conversion of L-cysteine to cysteine sulfinic acid (cysteine sulfinate). CDO plays an important role in cysteine catabolism, regulating intracellular levels of cysteine and responding changes in cysteine availability. As such, CDO is highly regulated and undergoes large changes in concentration and efficiency. It oxidizes cysteine to the corresponding sulfinic acid by activation of dioxygen, although the exact mechanism of the reaction is still unclear. In addition to being found in mammals, CDO also exists in some yeast and bacteria, although the exact function is still unknown. CDO has been implicated in various neurodegenerative diseases and cancers, which is likely related to cysteine toxicity. Function CDO is responsible for the first major step in metabolism of cysteine. CDO oxidizes to cysteine sulfinic acid (which exists predominantly in the anionic sulfinate form ''in vivo''). Overall, CDO catalyzes t ...
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2OG Oxygenase Inhibitors
Og ( he, עוֹג, ʿŌg ; ar, عوج, ʿŪj ; grc, Ωγ, Ōg) according to the Hebrew Bible and other sources, was an Amorite king of Bashan who was slain along with his army by Moses and his men at the battle of Edrei. In Arabic literature he is referred to as ʿŪj ibn ʿAnāq (). Og is introduced in the Book of Numbers. Like his neighbor Sihon of Heshbon, whom Moses had previously conquered at the battle of Jahaz, he was an Amorite king, the ruler of Bashan, which contained sixty walled cities and many unwalled towns, with his capital at Ashtaroth (probably modern Tell Ashtara, where there still exists a mound). The Book of Numbers, Chapter 21, and Deuteronomy, Chapter 3, continues: Next we turned and headed for the land of Bashan, where King Og and his entire army attacked us at Edrei. But the Lord told me, "Do not be afraid of him, for I have given you victory over Og and his entire army, and I will give you all his land. Treat him just as you treated King Sihon of ...
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Mildronate
Meldonium (INN; trade name Mildronate, among others) is a limited-market pharmaceutical, developed in 1970 by Ivars Kalviņš at the USSR Latvia Institute of Organic Synthesis, and now manufactured by the Latvian pharmaceutical company Grindeks and several generic manufacturers. It is primarily distributed in Eastern European countries as an anti- ischemia medication. Since 1 January 2016, it has been on the World Anti-Doping Agency (WADA) list of substances banned from use by athletes. Meldonium can be used as a metabolic modulator, changing how some hormones accelerate or slow down enzymatic reactions in the body. However, there are debates over its use as an athletic performance enhancer. Some athletes are known to have used meldonium before it was banned. Nevertheless, many athletes have been suspended or disqualified officially in relation to this drug. Medical use Meldonium may be used to treat coronary artery disease. These heart problems may sometimes lead to ...
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N-Oxalylglycine
''N''-Oxalylglycine is the organic compound with the formula HO2CC(O)NHCH2CO2H. This colourless solid is used as an inhibitor of α-ketoglutarate-dependent enzymes.Hausinger, R. P."Fe(II)/α-ketoglutarate-dependent hydroxylases and related enzymes" Critical Reviews of Biochemical Molecular Biology 2004, 39: pp 21-68. It is isosteric with α-ketoglutaric acid. Such enzymes are pervasive and, for example, are required for the synthesis of 4-hydroxyproline (2''S'',4''R'')-4-Hydroxyproline, or L-hydroxyproline ( C5 H9 O3 N), is an amino acid, abbreviated as Hyp or O, ''e.g.'', in Protein Data Bank. Structure and discovery In 1902, Hermann Emil Fischer isolated hydroxyproline from hydrolyzed gelatin. .... References {{DEFAULTSORT:Oxalylglycine, N- Carboxamides Dicarboxylic acids ...
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PHD2 Iron Binding Site
PHD or PhD may refer to: * Doctor of Philosophy (PhD), an academic qualification Entertainment * '' PhD: Phantasy Degree'', a Korean comic series * ''Piled Higher and Deeper'', a web comic * Ph.D. (band), a 1980s British group ** Ph.D. (Ph.D. album) * Ph.D. (Art Farmer album) * "PHD", a song on the album ''Tweekend'' by the Crystal Method Science and technology * PHD finger PHD or PhD may refer to: * Doctor of Philosophy (PhD), an academic qualification Entertainment * '' PhD: Phantasy Degree'', a Korean comic series * ''Piled Higher and Deeper ''Piled Higher and Deeper'' (also known as ''PhD Comics''), is a newsp ..., a protein sequence * Enzymes PHD1, PHD2 and PHD3 {{Disambiguation ...
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Isopenicillin N Synthase
Isopenicillin N synthase (IPNS) is a non-heme iron protein belongig to the 2-oxoglutarate (2OG)-dependent dioxygenases oxidoreductase family. This enzyme catalyzes the formation of isopenicillin N from δ-(L-α-aminoadipoyl)-L-cysteinyl-D-valine (LLD-ACV). :''N''- 5''S'')-5-amino-5-carboxypentanoylL-cysteinyl-D-valine + O2 \rightleftharpoons isopenicillin N + 2 H2O This reaction is a key step in the biosynthesis of penicillin and cephalosporin antibiotics. The active sites of most isopenicillin N synthases contain an iron ion. This enzyme is also called isopenicillin N synthetase. Mechanism A Fe(II) metal ion in the active site of the enzyme is coordinated by at least two histidine residues, an aspartate residue, a glutamine residue, and two water molecules in the absence of a bound substrate. Just two histidine residues and one aspartic acid residue are entirely conserved. Therefore, it is highly significant that these two histidine residues, His214 and His270, an ...
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EGLN1
Hypoxia-inducible factor prolyl hydroxylase 2 (HIF-PH2), or prolyl hydroxylase domain-containing protein 2 (PHD2), is an enzyme encoded by the ''EGLN1'' gene. It is also known as Egl nine homolog 1. PHD2 is a α-ketoglutarate/2-oxoglutarate-dependent hydroxylase, a superfamily non-haem iron-containing proteins. In humans, PHD2 is one of the three isoforms of hypoxia-inducible factor-proline dioxygenase, which is also known as HIF prolyl-hydroxylase. The hypoxia response HIF-1α is a ubiquitous, constitutively synthesized transcription factor responsible for upregulating the expression of genes involved in the cellular response to hypoxia. These gene products may include proteins such as glycolytic enzymes and angiogenic growth factors. In normoxia, HIF alpha subunits are marked for the ubiquitin-proteasome degradation pathway through hydroxylation of proline-564 and proline-402 by PHD2. Prolyl hydroxylation is critical for promoting pVHL binding to HIF, which targets HIF ...
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Jelly Roll Fold
The jelly roll or Swiss roll fold is a protein fold or supersecondary structure composed of eight beta strands arranged in two four-stranded sheets. The name of the structure was introduced by Jane S. Richardson in 1981, reflecting its resemblance to the jelly or Swiss roll cake. The fold is an elaboration on the Greek key motif and is sometimes considered a form of beta barrel. It is very common in viral proteins, particularly viral capsid proteins. Taken together, the jelly roll and Greek key structures comprise around 30% of the all-beta proteins annotated in the Structural Classification of Proteins (SCOP) database. Structure The basic jelly roll structure consists of eight beta strands arranged in two four-stranded antiparallel beta sheets which pack together across a hydrophobic interface here citation... uniprot The strands are traditionally labeled B through I for the historical reason that the first solved structure, of a jelly roll capsid protein from the toma ...
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Cytochrome P450
Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compounds, as well as for hormone synthesis and breakdown. In 1963, Estabrook, Cooper, and Rosenthal described the role of CYP as a catalyst in steroid hormone synthesis and drug metabolism. In plants, these proteins are important for the biosynthesis of defensive compounds, fatty acids, and hormones. CYP enzymes have been identified in all kingdoms of life: animals, plants, fungi, protists, bacteria, and archaea, as well as in viruses. However, they are not omnipresent; for example, they have not been found in ''Escherichia coli''. , more than 300,000 distinct CYP proteins are known. CYPs are, in general, the terminal oxidase enzymes in electron transfer chains, broadly categorized as P450-containing systems. The term "P450" is deriv ...
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Mechanism Of 2OG Oxygenases
Mechanism may refer to: * Mechanism (engineering), rigid bodies connected by joints in order to accomplish a desired force and/or motion transmission *Mechanism (biology), explaining how a feature is created *Mechanism (philosophy), a theory that all natural phenomena can be explained by physical causes * Mechanism (sociology), a theory that all social phenomena can be explained by the existence of a deterministic mechanism * " The Mechanism", song by Disclosure * ''The Mechanism'' (TV series), a Netflix TV series See also * Machine *Machine (mechanical) *Linkage (mechanical) *Mechanism design, the art of designing rules of a game to achieve a specific outcome *Mechanism of action, the means by which a drug exerts its biological effects *Defence mechanism, unconscious mechanisms aimed at reducing anxiety * Reaction mechanism, the sequence of reactions by which overall chemical change occurs *Antikythera mechanism, an ancient Greek analog computer *Theory of operation A theory ...
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