Samuelson J, Zhang W W, Kumar A, Descoteaux S, Shen P S, Bailey G
Department of Tropical Public Health, Harvard School of Public Health, Boston, MA 02115.
Arch Med Res. 1992;23(2):31-3.
Ethanol is the major metabolic product of glucose fermentation by the protozoan parasite E. histolytica under the anaerobic conditions found in the lumen of the colon. With the goal of finding new targets for anti-amebic drugs, the E. histolytica NADP(+)-dependent alcohol dehydrogenase gene (EhADH1; EC 1.1.1.2) and an aldehyde dehydrogenase gene (EhALDH1; EC 1.3.2) were cloned. The EhADH1 alcohol dehydrogenase gene encoded -39 kDa protein with 62 and 60% amino acid identities, respectively, with NADP(+)-dependent alcohol dehydrogenases of anaerobic bacteria Thermoanaerobium brockii and Clostridia beijerinckii. In contrast, EhADH1 showed a 15% amino acid identity with the closest human alcohol dehydrogenase. An EhADH1-glutathione-S-transferase fusion protein showed the expected NADP(+)-dependent alcohol dehydrogenase and NADPH-dependent acetaldehyde reductase activities. The enzymatic activities of the EhADH1 fusion protein were inhibited by pyrazole and 4-methyl pyrazole. The E. histolytica aldehyde dehydrogenase EhALDH1 gene encoded a 60 kDa protein, which showed a 36% amino acid identity over a 451 amino acid overlap with the human stomach aldehyde dehydrogenase (ALDH3).
乙醇是原生动物寄生虫溶组织内阿米巴在结肠腔内厌氧条件下葡萄糖发酵的主要代谢产物。为了寻找抗阿米巴药物的新靶点，克隆了溶组织内阿米巴NADP(+)-依赖性乙醇脱氢酶基因（EhADH1；EC 1.1.1.2）和醛脱氢酶基因（EhALDH1；EC 1.3.2）。EhADH1乙醇脱氢酶基因编码一种-39 kDa的蛋白质，与厌氧细菌布氏嗜热厌氧菌和拜氏梭菌的NADP(+)-依赖性乙醇脱氢酶的氨基酸同源性分别为62%和60%。相比之下，EhADH1与最接近的人类乙醇脱氢酶的氨基酸同源性为15%。一种EhADH1-谷胱甘肽-S-转移酶融合蛋白表现出预期的NADP(+)-依赖性乙醇脱氢酶和NADPH依赖性乙醛还原酶活性。EhADH1融合蛋白的酶活性受到吡唑和4-甲基吡唑的抑制。溶组织内阿米巴醛脱氢酶EhALDH1基因编码一种60 kDa的蛋白质，在451个氨基酸的重叠区域与人类胃醛脱氢酶（ALDH3）的氨基酸同源性为36%。
