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http://purl.uniprot.org/citations/25623425http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25623425http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25623425http://www.w3.org/2000/01/rdf-schema#comment"Prostacyclin synthase (CYP8A1) is an enzyme responsible for the biosynthesis of prostacyclin (PGI2) which inhibits platelet activation and exhibits anti-inflammatory effect. The objectives of this study were to identify CYP8A1 genetic variants and characterize functional consequences of CYP8A1 variants. In total, 27 variants including four previously unidentified single-nucleotide polymorphisms (SNPs) were identified by direct DNA sequencing in Koreans (n=48). Among them, CYP8A1 A447T and E314Stop were newly assigned as CYP8A1(∗)5 and CYP8A1(∗)6 by the Human Cytochrome P450 Allele Nomenclature Committee, respectively. CYP8A1(∗)5 was found in the heme binding area in three individuals as a heterozygous mutation. To investigate the functional change of CYP8A1(∗)5, CYP8A1(∗)5 and wild-type CYP8A1 protein were overexpressed in an Escherichia coli expression system and purified. Metabolism of PGH2 by the CYP8A1(∗)5 protein exhibited significantly decreased activity, resulting in a 45% decrease in Vmax and a 1.8-fold decrease in intrinsic clearance compared to the wild-type. Based on the predicted crystal structure of CYP8A1(∗)5 using the Molecular Operating Environment platform, the distance from CYP8A1 Cys441 to the heme was altered with a significantly changed binding free energy for the mutant protein. Further studies would be needed to determine the effect of CYP8A1(∗)5 on PGI2 levels in humans."xsd:string
http://purl.uniprot.org/citations/25623425http://purl.org/dc/terms/identifier"doi:10.1016/j.abb.2015.01.012"xsd:string
http://purl.uniprot.org/citations/25623425http://purl.org/dc/terms/identifier"doi:10.1016/j.abb.2015.01.012"xsd:string
http://purl.uniprot.org/citations/25623425http://purl.uniprot.org/core/author"Lee S.J."xsd:string
http://purl.uniprot.org/citations/25623425http://purl.uniprot.org/core/author"Lee S.J."xsd:string
http://purl.uniprot.org/citations/25623425http://purl.uniprot.org/core/author"Kim W.Y."xsd:string
http://purl.uniprot.org/citations/25623425http://purl.uniprot.org/core/author"Kim W.Y."xsd:string
http://purl.uniprot.org/citations/25623425http://purl.uniprot.org/core/author"Yi M."xsd:string
http://purl.uniprot.org/citations/25623425http://purl.uniprot.org/core/author"Yi M."xsd:string
http://purl.uniprot.org/citations/25623425http://purl.uniprot.org/core/author"Cho S.A."xsd:string
http://purl.uniprot.org/citations/25623425http://purl.uniprot.org/core/author"Cho S.A."xsd:string
http://purl.uniprot.org/citations/25623425http://purl.uniprot.org/core/author"Jarrar Y.B."xsd:string
http://purl.uniprot.org/citations/25623425http://purl.uniprot.org/core/author"Jarrar Y.B."xsd:string
http://purl.uniprot.org/citations/25623425http://purl.uniprot.org/core/author"Rohn-Glowacki K.J."xsd:string
http://purl.uniprot.org/citations/25623425http://purl.uniprot.org/core/author"Rohn-Glowacki K.J."xsd:string
http://purl.uniprot.org/citations/25623425http://purl.uniprot.org/core/author"Shin J.G."xsd:string
http://purl.uniprot.org/citations/25623425http://purl.uniprot.org/core/author"Shin J.G."xsd:string
http://purl.uniprot.org/citations/25623425http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/25623425http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/25623425http://purl.uniprot.org/core/name"Arch. Biochem. Biophys."xsd:string
http://purl.uniprot.org/citations/25623425http://purl.uniprot.org/core/name"Arch. Biochem. Biophys."xsd:string
http://purl.uniprot.org/citations/25623425http://purl.uniprot.org/core/pages"10-18"xsd:string
http://purl.uniprot.org/citations/25623425http://purl.uniprot.org/core/pages"10-18"xsd:string