Microsomal prostaglandin E synthase-2 (mPGES-2)[5][6]orProstaglandin E synthase 2 is an enzyme that in humans encoded by the PTGES2gene located on chromosome 9.[7][8] 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.[9]
Microsomal prostaglandin E synthase type-2 (mPTGES2) has been crystallized with an anti-inflammatory drug indomethacin (IMN).[10] 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.[10]
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.[13]
The PTGE2 protein also has been shown to activate the transcription regulated by an interferon-gamma gamma-interferon-activated transcription element (GATE).[8]
As such, pharmacological inhibition of prostaglandin E 2 production by synthetic minor prenylated chalcones and flavonoids has potential therapeutic viability.[14] It has been shown that the synthesis of prostaglandin E 2 in the endothelial cells of the brain is important for inflammation-induced fever.[18] Additionally, investigators have observed elevations in cell doubling rates for several cancer cell types in the presence of prostaglandin E 2 –producing cell lines.[19]
^Tanikawa N, Ohmiya Y, Ohkubo H, Hashimoto K, Kangawa K, Kojima M, Ito S, Watanabe K (Mar 2002). "Identification and characterization of a novel type of membrane-associated prostaglandin E synthase". Biochemical and Biophysical Research Communications. 291 (4): 884–9. doi:10.1006/bbrc.2002.6531. PMID11866447.
^ abYamada T, Komoto J, Watanabe K, Ohmiya Y, Takusagawa F (May 2005). "Crystal structure and possible catalytic mechanism of microsomal prostaglandin E synthase type 2 (mPGES-2)". Journal of Molecular Biology. 348 (5): 1163–76. doi:10.1016/j.jmb.2005.03.035. PMID15854652.
^Tanikawa N, Ohmiya Y, Ohkubo H, Hashimoto K, Kangawa K, Kojima M, Ito S, Watanabe K (2002). "Identification and characterization of a novel type of membrane-associated prostaglandin E synthase". Biochem. Biophys. Res. Commun. 291 (4): 884–9. doi:10.1006/bbrc.2002.6531. PMID11866447.
^Watanabe K, Ohkubo H, Niwa H, Tanikawa N, Koda N, Ito S, Ohmiya Y (2003). "Essential 110Cys in active site of membrane-associated prostaglandin E synthase-2". Biochem. Biophys. Res. Commun. 306 (2): 577–81. doi:10.1016/s0006-291x(03)01025-8. PMID12804604.
^Ruan D, So SP (Oct 2014). "Prostaglandin E2 produced by inducible COX-2 and mPGES-1 promoting cancer cell proliferation in vitro and in vivo". Life Sciences. 116 (1): 43–50. doi:10.1016/j.lfs.2014.07.042. PMID25139833.
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.
Fischer A, Grallert H, Böhme M, Gieger C, Boomgaarden I, Heid I, Wichmann HE, Döring F, Illig T (Apr 2009). "Association analysis between the prostaglandin E synthase 2 R298H polymorphism and body mass index in 8079 participants of the KORA study cohort". Genetic Testing and Molecular Biomarkers. 13 (2): 223–6. doi:10.1089/gtmb.2008.0111. PMID19371221.
Mattila S, Tuominen H, Koivukangas J, Stenbäck F (Apr 2009). "The terminal prostaglandin synthases mPGES-1, mPGES-2, and cPGES are all overexpressed in human gliomas". Neuropathology. 29 (2): 156–65. doi:10.1111/j.1440-1789.2008.00963.x. PMID19347995. S2CID22681905.
Lindner I, Helwig U, Rubin D, Fischer A, Marten B, Schreiber S, Döring F, Schrezenmeir J (Dec 2007). "Prostaglandin E synthase 2 (PTGES2) Arg298His polymorphism and parameters of the metabolic syndrome". Molecular Nutrition & Food Research. 51 (12): 1447–51. doi:10.1002/mnfr.200700144. PMID17979097.
Seo T, Tatsuguchi A, Shinji S, Yonezawa M, Mitsui K, Tanaka S, Fujimori S, Gudis K, Fukuda Y, Sakamoto C (Jun 2009). "Microsomal prostaglandin E synthase protein levels correlate with prognosis in colorectal cancer patients". Virchows Archiv. 454 (6): 667–76. doi:10.1007/s00428-009-0777-z. PMID19412621. S2CID6233883.
Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S (Jan 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC1347501. PMID16381901.
Oh JH, Yang JO, Hahn Y, Kim MR, Byun SS, Jeon YJ, Kim JM, Song KS, Noh SM, Kim S, Yoo HS, Kim YS, Kim NS (Dec 2005). "Transcriptome analysis of human gastric cancer". Mammalian Genome. 16 (12): 942–54. doi:10.1007/s00335-005-0075-2. PMID16341674. S2CID69278.
