Prostaglandin-I synthase (EC5.3.99.4) also known asprostaglandin I2 (prostacyclin) synthase (PTGIS) orCYP8A1 is anenzyme involved inprostanoid biosynthesis that in humans is encoded by thePTGISgene.[4] This enzyme belongs to the family ofcytochrome P450isomerases.
This gene encodes a member of thecytochrome P450 superfamily ofenzymes. The cytochrome P450 proteins aremonooxygenases 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. Thisendoplasmic reticulum membrane protein catalyzes the conversion ofprostaglandin H2 toprostacyclin (prostaglandin I2), a potent vasodilator and inhibitor ofplatelet aggregation. An imbalance of prostacyclin and its physiological antagonistthromboxane A2 contribute to the development ofmyocardial infarction,stroke, andatherosclerosis.[5]
Unlike most P450 enzymes, PGIS does not requiremolecular oxygen (O2). Instead it uses itsheme cofactor to catalyze the isomerization of prostaglandin H2 to prostacyclin. Prostaglandin H2 is produced bycyclooxygenase in the first committed step ofprostaglandin biosynthesis.
Thesystematic name of this enzyme class is(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate 6-isomerase. Other names in common use includeprostacyclin synthase,prostacyclin synthetase,prostagladin I2 synthetase,PGI2 synthase,PGIS,PTGIS, andPGI2 synthetase.
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 usingsurface plasmon resonance technology.[6]
Ullrich V, Castle L, Weber P (July 1981). "Spectral evidence for the cytochrome P450 nature of prostacyclin synthetase".Biochemical Pharmacology.30 (14):2033–2036.doi:10.1016/0006-2952(81)90218-5.PMID7023490.
Xie X, Ma YT, Fu ZY, Yang YN, Wang YH, Chen BD, et al. (June 2008). "[Study on the association of cyclooxygenase-2 -765g>C and prostacyclin synthase C1117A polymorphisms and the risk of myocardial infarction in Uigur population of Xinjiang, China]".Zhonghua Liu Xing Bing Xue Za Zhi = Zhonghua Liuxingbingxue Zazhi.29 (6):598–603.PMID19040046.
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.
Nelson DR, Zeldin DC, Hoffman SM, Maltais LJ, Wain HM, Nebert DW (January 2004). "Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants".Pharmacogenetics.14 (1):1–18.doi:10.1097/00008571-200401000-00001.PMID15128046.
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.
