Microsomal prostaglandin E synthase-2 (mPGES-2) or Prostaglandin E synthase 2 is an enzyme that in humans encoded by the ''PTGES2''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

located on

chromosome 9 Chromosome 9 is one of the 23 pairs of chromosomes in humans. Humans normally have two copies of this chromosome, as they normally do with all chromosomes. Chromosome 9 spans about 138 million base pairs of nucleic acids (the building blocks of DN ...

. The protein encoded by this gene is a membrane-associated

prostaglandin Prostaglandins (PG) are a group of physiology, physiologically active lipid compounds called eicosanoids that have diverse hormone-like effects in animals. Prostaglandins have been found in almost every Tissue (biology), tissue in humans and ot ...

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.

Structure

Microsomal prostaglandin E synthase type-2 (mPTGES2) has been crystallized with an

anti-inflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation, fever or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs reduce pain by inhibiting mechan ...

drug indomethacin (IMN). The N-terminal of mPTGES2 is attached to the lipid membrane and the two hydrophobic pockets connected to form a V shape are located in the bottom of a large cavity for IMN binding. The mPTGES2 exists in a

dimer Dimer may refer to: * Dimer (chemistry), a chemical structure formed from two similar sub-units ** Protein dimer, a protein quaternary structure ** d-dimer ** TH-dimer * Dimer model, an item in statistical mechanics, based on ''domino tiling'' * ...

Function

The gene encoding the PTGES2 protein contains 10

exons An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence i ...

. The PTGE2 protein encoded by the gene is a 33-kDa membrane-associated

prostaglandin E synthase Prostaglandin E synthase (, 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. The synthase generating PGE2 is a membrane-associate ...

that is thought to be targeted to the

Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic Cell (biology), cells. Part of the endomembrane system in the cytoplasm, it protein targeting, packages proteins ...

as well as the

mitochondrion A mitochondrion () is an organelle found in the cell (biology), cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosine tri ...

within the cell.

Prostaglandin E synthase Prostaglandin E synthase (, 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. The synthase generating PGE2 is a membrane-associate ...

catalyzes the conversion of

prostaglandin H2 Prostaglandin H2 (PGH2), or prostaglandin H2 (PGH2), is a type of prostaglandin and a precursor for many other biologically significant molecules. It is synthesized from arachidonic acid in a reaction catalyzed by a cyclooxygenase enzyme. The con ...

prostaglandin E2 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 pregnanc ...

. The particular reaction catalyzed by PTGE2 is thought to be: (5Z,13E)-(15S)-9-alpha,11-alpha-epidioxy-15-hydroxyprosta-5,13-dienoate = (5Z,13E)-(15S)-11-alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate. The PTGE2 protein functions in part of the prostaglandin synthesis pathway, which forms a component of the overall lipid synthesis mechanism in the human body. The activity of PTGES2 is thought to be increased in the presence of

sulfhydryl In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl grou ...

compounds, in particular

dithiothreitol Dithiothreitol (DTT) is an organosulfur compound with the formula . A colorless compound, it is classified as a dithiol and a diol. DTT is redox reagent also known as Cleland's reagent, after W. Wallace Cleland. The reagent is commonly used in ...

. The PTGE2 protein also has been shown to activate the transcription regulated by an

interferon-gamma Interferon gamma (IFNG or IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. ...

gamma-interferon-activated transcription element (GATE).

Clinical significance

The excess production of prostaglandin E 2 is known to contribute to inflammatory diseases which includes

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...

, and

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

. Furthermore, naturally occurring polymorphisms of PTGES2 have been shown to be associated with increased risks for

diabetes mellitus Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained hyperglycemia, high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or th ...

and

metabolic syndrome Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Metabolic syndro ...

s. As such, pharmacological inhibition of prostaglandin E 2 production by synthetic minor prenylated chalcones and flavonoids has potential therapeutic viability. It has been shown that the synthesis of prostaglandin E 2 in the

endothelial cells The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the res ...

of the brain is important for inflammation-induced fever. Additionally, investigators have observed elevations in cell doubling rates for several cancer cell types in the presence of prostaglandin E 2 –producing cell lines.

Structure

Function

Clinical significance

References

External links

Further reading