title: Characterization of thioredoxin reductase genes (trr1) from Pneumocystis carinii and Pneumocystis jiroveci.
abstract: We have characterized the thioredoxin reductase (trr1) genes from Pneumocystis carinii and Pneumocystis jiroveci, and have demonstrated that multiple copies of an approximately 500 base pair fragment of the trr1 gene are present in P. carinii, but not in P. jiroveci. Thioredoxin reductases encoded by the full-length genes have predicted molecular weights of approximately 35,000 and show high homology to yeast Trr1. An NADPH-binding domain with a putative redox active site CAVC as well as an flavin-adenine dinucleotide-binding domain are highly conserved in both proteins, which were 85% identical. The multicopy trr1 gene fragments in P. carinii are not transcribed or expressed. Duplication of the gene fragment likely occurred in conjunction with duplication of the kexin homologue, protease-1, which is located immediately upstream of the trr1 gene. Thioredoxin reductase, an enzyme implicated in the growth, survival and pathogenicity of certain microbes, could be a potential target for therapeutic intervention in Pneumocystis infection.
authors.affiliation: Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Building 10, Room 7D43, MSC 1662, Bethesda, MD 20892-1662, USA.
authors.forename: Geetha
authors.initials: G
authors.lastname: Kutty
authors.forename: Sheng N
authors.initials: SN
authors.lastname: Huang
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kovacs
mesh_terms: D000595:Amino Acid Sequence; D001203:Ascomycota / Q000201:enzymology / Q000235:genetics*; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D008969:Molecular Sequence Data; D011010:Pneumocystis / Q000201:enzymology / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D012568:Schizosaccharomyces / Q000201:enzymology / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics* / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D004271:DNA, Fungal; D005656:Fungal Proteins; C476057:TRR1 protein, Pneumocystis carinii; C476058:TRR1 protein, Pneumocystis jirovecii; D013880:Thioredoxin-Disulfide Reductase