Kutty Geetha, Huang Sheng N, Kovacs Joseph A
Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Building 10, Room 7D43, MSC 1662, Bethesda, MD 20892-1662, USA.
Gene. 2003 May 22;310:175-83. doi: 10.1016/s0378-1119(03)00549-3.
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.
我们已对卡氏肺孢子菌和耶氏肺孢子菌的硫氧还蛋白还原酶（trr1）基因进行了特征分析，并证实trr1基因约500个碱基对的片段在卡氏肺孢子菌中有多个拷贝，但在耶氏肺孢子菌中则没有。由全长基因编码的硫氧还蛋白还原酶预测分子量约为35,000，并且与酵母Trr1具有高度同源性。两种蛋白质中具有推定氧化还原活性位点CAVC的NADPH结合结构域以及黄素腺嘌呤二核苷酸结合结构域高度保守，二者有85%的同一性。卡氏肺孢子菌中的多拷贝trr1基因片段不转录或表达。基因片段的复制可能与位于trr1基因紧邻上游的克新同源物蛋白酶-1的复制同时发生。硫氧还蛋白还原酶是一种与某些微生物的生长、存活和致病性有关的酶，可能是肺孢子菌感染治疗干预的潜在靶点。
