MPGES-2

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Lua error in Module:Infobox_gene at line 53: attempt to index field 'wikibase' (a nil value). Microsomal prostaglandin E synthase-2 (mPGES-2)[1][2] or Prostaglandin E synthase 2 is an enzyme that in humans encoded by the PTGES2 gene located on chromosome 9.[3][4] 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.[5]

Structure

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Microsomal prostaglandin E synthase type-2 (mPTGES2) has been crystallized with an anti-inflammatory drug indomethacin (IMN).[6] 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.[6]

Function

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The gene encoding the PTGES2 protein contains 10 exons. The PTGE2 protein encoded by the gene is a 33-kDa membrane-associated [7] prostaglandin E synthase that is thought to be targeted to the Golgi apparatus as well as the mitochondrion within the cell. Prostaglandin E synthase catalyzes the conversion of prostaglandin H2 to prostaglandin E2. 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.[8]

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 compounds, in particular dithiothreitol.[9]

The PTGE2 protein also has been shown to activate the transcription regulated by an interferon-gamma gamma-interferon-activated transcription element (GATE).[4]

Clinical significance

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The excess production of prostaglandin E 2 is known to contribute to inflammatory diseases which includes rheumatoid arthritis, atherosclerosis, and cancer.[10][11] Furthermore, naturally occurring polymorphisms of PTGES2 have been shown to be associated with increased risks for diabetes mellitus and metabolic syndromes.[12][13]

As such, pharmacological inhibition of prostaglandin E 2 production by synthetic minor prenylated chalcones and flavonoids has potential therapeutic viability.[10] It has been shown that the synthesis of prostaglandin E 2 in the endothelial cells of the brain is important for inflammation-induced fever.[14] Additionally, investigators have observed elevations in cell doubling rates for several cancer cell types in the presence of prostaglandin E 2 –producing cell lines.[15]

References

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  9. ^ The gene encoding the PTGES2 protein contains 10 exons. The PTGE2 protein is a membrane-associated prostaglandin E synthase. Prostaglandin E synthase catalyzes the conversion of prostaglandin H2 to prostaglandin E2. The particular reaction catalyzed by PTGE2 is thought to be:
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  • Overview of all the structural information available in the PDB for UniProt: Q9N0A4 (Macaca fascicularis (Crab-eating macaque)Prostaglandin E synthase 2) at the PDBe-KB.

Further reading

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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