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首页> 美国卫生研究院文献>Drug Target Insights >Molecular and Kinetic Characterization of Babesia microti Gray Strain Lactate Dehydrogenase as a Potential Drug Target
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Molecular and Kinetic Characterization of Babesia microti Gray Strain Lactate Dehydrogenase as a Potential Drug Target

机译：巴贝斯小虫灰色菌株乳酸脱氢酶作为潜在药物靶标的分子和动力学表征。

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Babesia microti is an emerging zoonotic protozoan organism that causes “malaria-like” symptoms that can be fatal in immunocompromised people. Owing to lack of specific therapeutic regiment against the disease, we cloned and characterized B. microti lactate dehydrogenase (BmLDH) as a potential molecular drug receptor. The in vitro kinetic properties of BmLDH enzyme was evaluated using nicotinamide adenine dinucleotide (NAD+) as a co-factor and lactate as a substrate. Inhibitory assay was also done using gossypol as BmLDH inhibitor to determine the inhibitory concentration 50 (IC50). The result showed that the 0.99 kbp BmLDH gene codes for a barely soluble 36 kDa protein (332 amino acids) localized in both the cytoplasm and nucleus of the parasite. In vitro enzyme kinetic studies further revealed that BmLDH is an active enzyme with a high catalytic efficiency at optimal pH of 10.2. The Km values of NAD+ and lactate were 8.7 ± 0.57 mM and 99.9 ± 22.33 mM, respectively. The IC50 value for gossypol was 0.345 μM, while at 2.5 μM, gossypol caused 100% inhibition of BmLDH catalytic activity. These findings, therefore, provide initial evidence that BmLDH could be a potential drug target, although further in vivo studies are needed to validate the practical application of lactate dehydrogenase inhibitors against B. microti infection.
机译：小巴贝虫是一种新兴的人畜共患的原生动物生物，会引起“类疟疾”症状，这些症状在免疫力低下的人中可能致命。由于缺乏针对该疾病的特异性治疗方案，我们克隆并鉴定了小肠芽孢杆菌乳酸脱氢酶（BmLDH）作为潜在的分子药物受体。以烟酰胺腺嘌呤二核苷酸（NAD + ）为辅因子，乳酸为底物，评价BmLDH酶的体外动力学性质。还使用棉酚作为BmLDH抑制剂进行了抑制分析，以确定抑制浓度50（IC50）。结果表明，0.99 kbp BmLDH基因编码一种几乎不溶的36 kDa蛋白（332个氨基酸），位于寄生虫的细胞质和细胞核中。体外酶动力学研究进一步表明，BmLDH是一种活性酶，在最佳pH为10.2时具有很高的催化效率。 NAD + 和乳酸的Km值分别为8.7±0.57 mM和99.9±22.33 mM。棉酚的IC50值为0.345μM，而在2.5μM时，棉酚引起BmLDH催化活性的100％抑制。因此，这些发现提供了BmLDH可能成为潜在药物靶点的初步证据，尽管还需要进一步的体内研究来验证乳酸脱氢酶抑制剂对小肠杆状芽孢杆菌感染的实际应用。

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