Castillo-Villanueva Adriana, Méndez Sara Teresa, Torres-Arroyo Angélica, Reyes-Vivas Horacio, Oria-Hernández Jesús
Laboratorio de Bioquímica-Genética, Instituto Nacional de Pediatría, Secretaría de Salud. Av. Insurgentes Sur 3700 C, Insurgentes Cuicuilco, Delegación Coyoacán, 04530, Mexico, DF, Mexico.
Protein J. 2016 Feb;35(1):24-33. doi: 10.1007/s10930-015-9643-9.
The NADH oxidase family of enzymes catalyzes the oxidation of NADH by reducing molecular O2 to H2O2, H2O or both. In the protozoan parasite Giardia lamblia, the NADH oxidase enzyme (GlNOX) produces H2O as end product without production of H2O2. GlNOX has been implicated in the parasite metabolism, the intracellular redox regulation and the resistance to drugs currently used against giardiasis; therefore, it is an interesting protein from diverse perspectives. In this work, the GlNOX gene was amplified from genomic G. lamblia DNA and expressed in Escherichia coli as a His-Tagged protein; then, the enzyme was purified by immobilized metal affinity chromatography, characterized, and its properties compared with those of the endogenous enzyme previously isolated from trophozoites (Brown et al. in Eur J Biochem 241(1):155-161, 1996). In comparison with the trophozoite-extracted enzyme, which was scarce and unstable, the recombinant heterologous expression system and one-step purification method produce a stable protein preparation with high yield and purity. The recombinant enzyme mostly resembles the endogenous protein; where differences were found, these were attributable to methodological discrepancies or artifacts. This homogenous, pure and functional protein preparation can be used for detailed structural or functional studies of GlNOX, which will provide a deeper understanding of the biology and pathogeny of G. lamblia.
NADH氧化酶家族的酶通过将分子氧还原为过氧化氢、水或两者来催化NADH的氧化。在原生动物寄生虫蓝氏贾第鞭毛虫中,NADH氧化酶(GlNOX)产生水作为终产物,不产生过氧化氢。GlNOX与寄生虫代谢、细胞内氧化还原调节以及对目前用于治疗贾第虫病的药物的抗性有关;因此,从多个角度来看,它都是一种有趣的蛋白质。在这项工作中,从蓝氏贾第鞭毛虫基因组DNA中扩增出GlNOX基因,并在大肠杆菌中作为His标签蛋白表达;然后,通过固定化金属亲和色谱法纯化该酶,对其进行表征,并将其性质与先前从滋养体中分离出的内源性酶的性质进行比较(Brown等人,《欧洲生物化学杂志》241(1):155 - 161,1996)。与从滋养体中提取的稀少且不稳定的酶相比,重组异源表达系统和一步纯化方法产生了高产率和高纯度的稳定蛋白质制剂。重组酶大多类似于内源性蛋白质;发现差异时,这些差异可归因于方法学上的差异或人为因素。这种同质、纯净且具有功能的蛋白质制剂可用于对GlNOX进行详细的结构或功能研究,这将有助于更深入地了解蓝氏贾第鞭毛虫的生物学和发病机制。