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首页> 外文期刊>International Journal of Molecular Sciences >Functional and Biochemical Characterization of Three Recombinant Human Glucose-6-Phosphate Dehydrogenase Mutants: Zacatecas, Vanua-Lava and Viangchan
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Functional and Biochemical Characterization of Three Recombinant Human Glucose-6-Phosphate Dehydrogenase Mutants: Zacatecas, Vanua-Lava and Viangchan

机译：三种重组人葡萄糖-6-磷酸脱氢酶突变体的功能和生化特性：Zacatecas，Vanua-Lava和Viangchan

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摘要

Glucose-6-phosphate dehydrogenase (G6PD) deficiency in humans causes severe disease, varying from mostly asymptomatic individuals to patients showing neonatal jaundice, acute hemolysis episodes or chronic nonspherocytic hemolytic anemia. In order to understand the effect of the mutations in G6PD gene function and its relation with G6PD deficiency severity, we report the construction, cloning and expression as well as the detailed kinetic and stability characterization of three purified clinical variants of G6PD that present in the Mexican population: G6PD Zacatecas (Class I), Vanua-Lava (Class II) and Viangchan (Class II). For all the G6PD mutants, we obtained low purification yield and altered kinetic parameters compared with Wild Type (WT). Our results show that the mutations, regardless of the distance from the active site where they are located, affect the catalytic properties and structural parameters and that these changes could be associated with the clinical presentation of the deficiency. Specifically, the structural characterization of the G6PD Zacatecas mutant suggests that the R257L mutation have a strong effect on the global stability of G6PD favoring an unstable active site. Using computational analysis, we offer a molecular explanation of the effects of these mutations on the active site.
机译：人体中的6-磷酸葡萄糖脱氢酶（G6PD）缺乏会导致严重疾病，从无症状的个体到表现出新生儿黄疸，急性溶血发作或慢性非球囊性溶血性贫血的患者不等。为了了解G6PD基因功能突变的影响及其与G6PD缺乏症严重程度的关系，我们报道了墨西哥存在的三种纯化的G6PD临床变体的构建，克隆和表达以及详细的动力学和稳定性表征。人口：G6PD Zacatecas（I类），Vanua-Lava（II类）和Viangchan（II类）。对于所有G6PD突变体，与野生型（WT）相比，我们获得了较低的纯化产率并改变了动力学参数。我们的结果表明，该突变，无论与它们位于活性位点之间的距离如何，都会影响催化性能和结构参数，并且这些变化可能与缺陷的临床表现有关。具体来说，G6PD Zacatecas突变体的结构特征表明，R257L突变对G6PD的整体稳定性具有强烈的影响，有利于不稳定的活性位点。使用计算分析，我们提供了这些突变对活性位点影响的分子解释。

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