Prostaglandin E synthase

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prostaglandin-E synthase
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human microsomal prostaglandin E synthase 1 with bound glutathione. PDB entry 3DWW [1]
Identifiers
EC no. 5.3.99.3
CAS no. 52227-79-9
Databases
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ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / QuickGO
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NCBI proteins

Prostaglandin E synthase (EC 5.3.99.3, or PGE synthase) is an enzyme involved in eicosanoid and glutathione metabolism, a member of MAPEG family. It generates prostaglandin E (PGE) from prostaglandin H2. [2] [3]

Contents

The synthase generating PGE2 is a membrane-associated protein.

Biosynthesis of eicosanoids. Eicosanoid synthesis.svg
Biosynthesis of eicosanoids.

Isozymes

Humans express three prostaglandin-E synthase isozymes, each encoded by a separate gene:

prostaglandin E synthase (microsomal)
Identifiers
Symbol PTGES
Alt. symbolsMGST1L1
NCBI gene 9536
HGNC 9599
OMIM 605172
RefSeq NM_004878
UniProt O14684
Other data
Locus Chr. 9 q34.3
Search for
Structures Swiss-model
Domains InterPro
prostaglandin E synthase 2 (microsomal)
Identifiers
Symbol PTGES2
Alt. symbolsC9orf15
NCBI gene 80142
HGNC 17822
OMIM 608152
RefSeq NM_198939
UniProt Q9H7Z7
Other data
Locus Chr. 9 q34.12
Search for
Structures Swiss-model
Domains InterPro
prostaglandin E synthase 3 (cytosolic)
Identifiers
Symbol PTGES3
Alt. symbolsp23, TEBP, cPGES
NCBI gene 10728
HGNC 16049
OMIM 607061
RefSeq NM_006601
UniProt Q15185
Other data
Locus Chr. 12 q13.13
Search for
Structures Swiss-model
Domains InterPro

Related Research Articles

<span class="mw-page-title-main">Prostaglandin</span> Group of physiologically active lipid compounds

Prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derived enzymatically from the fatty acid arachidonic acid. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring. They are a subclass of eicosanoids and of the prostanoid class of fatty acid derivatives.

<span class="mw-page-title-main">Eicosanoid</span> Class of compounds

Eicosanoids are signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid or other polyunsaturated fatty acids (PUFAs) that are, similar to arachidonic acid, around 20 carbon units in length. Eicosanoids are a sub-category of oxylipins, i.e. oxidized fatty acids of diverse carbon units in length, and are distinguished from other oxylipins by their overwhelming importance as cell signaling molecules. Eicosanoids function in diverse physiological systems and pathological processes such as: mounting or inhibiting inflammation, allergy, fever and other immune responses; regulating the abortion of pregnancy and normal childbirth; contributing to the perception of pain; regulating cell growth; controlling blood pressure; and modulating the regional flow of blood to tissues. In performing these roles, eicosanoids most often act as autocrine signaling agents to impact their cells of origin or as paracrine signaling agents to impact cells in the proximity of their cells of origin. Eicosanoids may also act as endocrine agents to control the function of distant cells.

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Thromboxane A synthase 1 , also known as TBXAS1, is a cytochrome P450 enzyme that, in humans, is encoded by the TBXAS1 gene.

Prostaglandin E<sub>2</sub> Chemical compound

Prostaglandin E2 (PGE2), also known as dinoprostone, is a naturally occurring prostaglandin with oxytocic properties that is used as a medication. Dinoprostone is used in labor induction, bleeding after delivery, termination of pregnancy, and in newborn babies to keep the ductus arteriosus open. In babies it is used in those with congenital heart defects until surgery can be carried out. It is also used to manage gestational trophoblastic disease. It may be used within the vagina or by injection into a vein.

<span class="mw-page-title-main">Prostacyclin synthase</span>

Prostaglandin-I synthase also known as prostaglandin I2 (prostacyclin) synthase (PTGIS) or CYP8A1 is an enzyme involved in prostanoid biosynthesis that in humans is encoded by the PTGIS gene. This enzyme belongs to the family of cytochrome P450 isomerases.

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Prostaglandin-H2 D-isomerase (PTGDS) is an enzyme that in humans is encoded by the PTGDS gene.

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Prostaglandin-endoperoxide synthase 2, also known as cyclooxygenase-2 or COX-2, is an enzyme that in humans is encoded by the PTGS2 gene. In humans it is one of two cyclooxygenases. It is involved in the conversion of arachidonic acid to prostaglandin H2, an important precursor of prostacyclin, which is expressed in inflammation.

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Prostaglandin E2 receptor 4 (EP4) is a prostaglandin receptor for prostaglandin E2 (PGE2) encoded by the PTGER4 gene in humans; it is one of four identified EP receptors, the others being EP1, EP2, and EP3, all of which bind with and mediate cellular responses to PGE2 and also, but generally with lesser affinity and responsiveness, certain other prostanoids (see Prostaglandin receptors). EP4 has been implicated in various physiological and pathological responses in animal models and humans.

<span class="mw-page-title-main">PTGS1</span>

Cyclooxygenase 1 (COX-1), also known as prostaglandin G/H synthase 1, prostaglandin-endoperoxide synthase 1 or prostaglandin H2 synthase 1, is an enzyme that in humans is encoded by the PTGS1 gene. In humans it is one of two cyclooxygenases.

Prostaglandin EP<sub>1</sub> receptor Protein-coding gene in the species Homo sapiens

Prostaglandin E2 receptor 1 (EP1) is a 42kDa prostaglandin receptor encoded by the PTGER1 gene. EP1 is one of four identified EP receptors, EP1, EP2, EP3, and EP4 which bind with and mediate cellular responses principally to prostaglandin E2) (PGE2) and also but generally with lesser affinity and responsiveness to certain other prostanoids (see Prostaglandin receptors). Animal model studies have implicated EP1 in various physiological and pathological responses. However, key differences in the distribution of EP1 between these test animals and humans as well as other complicating issues make it difficult to establish the function(s) of this receptor in human health and disease.

Prostaglandin EP<sub>2</sub> receptor Protein-coding gene in the species Homo sapiens

Prostaglandin E2 receptor 2, also known as EP2, is a prostaglandin receptor for prostaglandin E2 (PGE2) encoded by the human gene PTGER2: it is one of four identified EP receptors, the others being EP1, EP3, and EP4, which bind with and mediate cellular responses to PGE2 and also, but with lesser affinity and responsiveness, certain other prostanoids (see Prostaglandin receptors). EP has been implicated in various physiological and pathological responses.

Prostaglandin EP<sub>3</sub> receptor Protein-coding gene in the species Homo sapiens

Prostaglandin EP3 receptor (53kDa), also known as EP3, is a prostaglandin receptor for prostaglandin E2 (PGE2) encoded by the human gene PTGER3; it is one of four identified EP receptors, the others being EP1, EP2, and EP4, all of which bind with and mediate cellular responses to PGE2 and also, but generally with lesser affinity and responsiveness, certain other prostanoids (see Prostaglandin receptors). EP has been implicated in various physiological and pathological responses.

<span class="mw-page-title-main">MAPEG family</span>

In molecular biology the MAPEG family of proteins are a group of membrane associated proteins with highly divergent functions. Included are the 5-lipoxygenase-activating protein, leukotriene C4 synthase, which catalyzes the production of leukotriene C4 (LTC4) from leukotriene A4 (LTA4), and microsomal glutathione S-transferase II (GST-II), which also produces LTC4 from LTA4.

<span class="mw-page-title-main">CYP4F8</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450 4F8 is a protein that in humans is encoded by the CYP4F8 gene.

<span class="mw-page-title-main">MPGES-1</span> Protein-coding gene in the species Homo sapiens

Microsomal prostaglandin E synthase-1 (mPGES-1) or Prostaglandin E synthase is an enzyme that in humans is encoded by the PTGES gene.

<span class="mw-page-title-main">Sulprostone</span> Chemical compound

Sulprostone is an analogue of prostaglandin E2 (PGE2) that has oxytocic activity in assays of rat kidney cells and tissues. There are four known receptors which mediate various but often different cellular and tissue responses to PGE2: prostaglandin EP1 receptor, prostaglandin EP2 receptor, prostaglandin EP3 receptor, and prostaglandin EP4 receptor. Sulprosotone binds to and activates the prostaglandin EP3 receptor with far greater efficacy than the other PGE2 receptors and also has the advantage of being relatively resistant, compared with PGE2, to becoming metabolically degraded. It is listed as a comparatively weak receptor agonist of the prostaglandin EP1 receptor. In all events, this as well as other potent synthetic EP3 receptor antagonists have the realized or potential ability to promote the beneficial effects of prostaglandin EP3 receptor activation.

<span class="mw-page-title-main">MPGES-2</span> Protein-coding gene in the species Homo sapiens

Microsomal prostaglandin E synthase-2 (mPGES-2) or Prostaglandin E synthase 2 is an enzyme that in humans encoded by the PTGES2 gene located on chromosome 9. The protein encoded by this gene is a membrane-associated prostaglandin E synthase, which catalyzes the conversion of prostaglandin H2 to prostaglandin E2. This protein also has been shown to activate the transcription regulated by a gamma-interferon-activated transcription element (GATE). Multiple transcript variants have been found for this gene.

The prostaglandin E2 (PGE2) receptors are G protein-coupled receptors that bind and are activated by prostaglandin E2. They are members of the prostaglandin receptors class of receptors and include the following Protein isoforms:

References

  1. Jegerschold, C.; Pawelzik, S. -C.; Purhonen, P.; Bhakat, P.; Gheorghe, K. R.; Gyobu, N.; Mitsuoka, K.; Morgenstern, R.; Jakobsson, P. -J.; Hebert, H. (2008). "Structural basis for induced formation of the inflammatory mediator prostaglandin E2". Proceedings of the National Academy of Sciences. 105 (32): 11110–11115. Bibcode:2008PNAS..10511110J. doi: 10.1073/pnas.0802894105 . PMC   2516235 . PMID   18682561.
  2. Murakami M, Nakatani Y, Tanioka T, Kudo I (August 2002). "Prostaglandin E synthase". Prostaglandins Other Lipid Mediat. 68–69: 383–99. doi:10.1016/S0090-6980(02)00043-6. PMID   12432931. S2CID   22246484.
  3. Park JY, Pillinger MH, Abramson SB (June 2006). "Prostaglandin E2 synthesis and secretion: the role of PGE2 synthases". Clin. Immunol. 119 (3): 229–40. doi:10.1016/j.clim.2006.01.016. PMID   16540375.