title: Bacterial and algal orthologs of prostaglandin H₂synthase: novel insights into the evolution of an integral membrane protein.
abstract: Prostaglandin H₂synthase (PGHS; EC 1.14.99.1), a bi-functional heme enzyme that contains cyclooxygenase and peroxidase activities, plays a central role in the inflammatory response, pain, and blood clotting in higher eukaryotes. In this review, we discuss the progenitors of the mammalian enzyme by using modern bioinformatics and homology modeling to draw comparisons between this well-studied system and its orthologs from algae and bacterial sources. A clade of bacterial and algal orthologs is described that have salient structural features distinct from eukaryotic counterparts, including the lack of a dimerization and EGF-like domains, the absence of gene duplicates, and minimal membrane-binding domains. The functional implications of shared and variant features are discussed.
authors.affiliation: Department of Biochemistry & Biophysics, Perelman School of Medicine, University of Pennsylvania, 242 Anatomy-Chemistry Building, Philadelphia, PA 19104, USA.
authors.forename: Kushol
authors.initials: K
authors.lastname: Gupta
authors.affiliation: Chemistry Department, Villanova University, Villanova, PA 19085, USA. Electronic address: barry.selinsky@villanova.edu.
authors.forename: Barry S
authors.initials: BS
authors.lastname: Selinsky
mesh_terms: D020418:Algal Proteins / Q000737:chemistry / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry / Q000145:classification / Q000235:genetics*; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: D020418:Algal Proteins; D001426:Bacterial Proteins; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases
keywords: Cyclooxygenase; Heme; Membrane binding; Myeloperoxidase; Peroxidase; Prostaglandin synthase; α-Dioxygenase