Prostaglandin-I synthase (EC5.3.99.4) also known as prostaglandin I2 (prostacyclin) synthase (PTGIS) or CYP8A1 is an enzyme involved in prostanoid biosynthesis that in humans is encoded by the PTGISgene.[4] This enzyme belongs to the family of cytochrome P450isomerases.
Function
This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. However, this protein is considered a member of the cytochrome P450 superfamily on the basis of sequence similarity rather than functional similarity. This endoplasmic reticulum membrane protein catalyzes the conversion of prostaglandin H2 to prostacyclin (prostaglandin I2), a potent vasodilator and inhibitor of platelet aggregation. An imbalance of prostacyclin and its physiological antagonist thromboxane A2 contribute to the development of myocardial infarction, stroke, and atherosclerosis.[5]
Unlike most P450 enzymes, PGIS does not require molecular oxygen (O2). Instead it uses its heme cofactor to catalyze the isomerization of prostaglandin H2 to prostacyclin. Prostaglandin H2 is produced by cyclooxygenase in the first committed step of prostaglandin biosynthesis.
Nomenclature
The systematic name of this enzyme class is (5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate 6-isomerase. Other names in common use include prostacyclin synthase, prostacyclin synthetase, prostagladin I2 synthetase, PGI2 synthase, PGIS, PTGIS, and PGI2 synthetase.
Pathways
Thromboxane synthesis
Eicosanoid synthesis.
Molecular interactions
Generally, protein–protein interactions play crucial roles and are critical for formation of protein microenvironment, cell signaling and direct regulation of the activity of metabolic enzymes. Information on tissue-specific spectrum of molecular interactions of prostacyclin synthase will be useful for subnetwork analysis of PTGIS. Following proteins became known as potential direct binders of PTGIS: CYP2J2, GST, GSTA1, GLRX3, AKR1A1. Protein–protein and protein-peptide interactions were experimentally verified using surface plasmon resonance technology.[6]
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Xie X, Ma YT, Fu ZY, Yang YN, Ma X, Wang YH, et al. (March 2009). "[Association of GLu461ALa polymorphism of prostacyclin synthase gene with myocardial infarction in Uigur population]". Zhonghua Yu Fang Yi Xue Za Zhi [Chinese Journal of Preventive Medicine]. 43 (3): 237–241. PMID19534932.
Xie X, Ma Y, Fu Z, Yang Y, Wang Y, Chen B, et al. (December 2008). "[Association of polymorphism of the prostacyclin synthase gene with myocardial infarction in Uigur population of Xinjiang]". Zhonghua Yi Xue Yi Chuan Xue Za Zhi = Zhonghua Yixue Yichuanxue Zazhi = Chinese Journal of Medical Genetics. 25 (6): 708–711. PMID19065539.
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Xie X, Ma YT, Fu ZY, Yang YN, Ma X, Chen BD, et al. (2009). "Association of polymorphisms of PTGS2 and CYP8A1 with myocardial infarction". Clinical Chemistry and Laboratory Medicine. 47 (3): 347–352. doi:10.1515/CCLM.2009.078. PMID19327107. S2CID30117064.
Ruan KH, Wu J, Cervantes V (January 2008). "Characterization of the substrate mimic bound to engineered prostacyclin synthase in solution using high-resolution NMR spectroscopy and mutagenesis: implication of the molecular mechanism in biosynthesis of prostacyclin". Biochemistry. 47 (2): 680–688. doi:10.1021/bi701671q. PMID18081314.
Hashimoto K, Ishibashi K, Gebretsadik T, Hartert TV, Yamamoto A, Nakayama T, et al. (November 2008). "Functional polymorphism of the promoter region of the prostacyclin synthase gene and severity of RSV infection in hospitalized children". Journal of Medical Virology. 80 (11): 2015–2022. doi:10.1002/jmv.21318. PMID18814254. S2CID6010576.
Ma YT, Xie X, Fu ZY, Yang YN, Ma X, Wang YH, et al. (February 2009). "[Haplotypes analysis of the prostacyclin synthase gene and myocardial infarction in Uigur population]". Zhonghua Xin Xue Guan Bing Za Zhi. 37 (2): 115–119. PMID19719985.
