A trade off between catalytic activity and protein stability determines the clinical manifestations of glucose-6-phosphate dehydrogenase (G6PD) deficiency.
A trade off between catalytic activity and protein stability determines the clinical manifestations of glucose-6-phosphate dehydrogenase (G6PD) deficiency.
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DOI：
10.1016/j.ijbiomac.2017.06.002
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发表时间：
2017-11
影响因子：
8.2
通讯作者：
Imwong M
中科院分区：
文献类型：
--
作者：
Boonyuen U;Chamchoy K;Swangsri T;Junkree T;Day NPJ;White NJ;Imwong M
葡萄糖 - 6 - 磷酸脱氢酶（G6PD）缺乏症是人类最常见的多态性和酶病，全球约有4亿人受其影响。它可导致多种临床表现，包括蚕豆病、溶血性贫血、慢性非球形红细胞溶血性贫血、自然流产以及新生儿高胆红素血症。了解G6PD缺乏症严重程度的分子机制非常重要，但许多G6PD变异体的相关机制仍不清楚。在本研究中，我们报告了五种临床G6PD变异体——G6PD曼谷型、G6PD曼谷noi型、G6PD宋卡那拉因德型、G6PD广州 + 曼谷noi型以及G6PD联合 + 万象型的构建、表达、纯化以及在动力学特性和稳定性方面的生化特征。与天然G6PD相比，G6PD曼谷型和G6PD广州 + 曼谷noi型显示出催化活性完全丧失以及热稳定性适度降低。G6PD曼谷noi型和G6PD联合 + 万象型显示催化效率显著降低，而G6PD宋卡那拉因德型显示出与野生型酶相当的催化活性。联合 + 万象突变对酶的整体稳定性有显著影响。此外，我们的结果表明，G6PD变异体中突变的位置会影响其催化活性、稳定性和结构。因此，我们的结果为G6PD缺乏症患者的临床表现提供了分子层面的解释。
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common polymorphism and enzymopathy in humans, affecting approximately 400 million people worldwide. It is responsible for various clinical manifestations, including favism, hemolytic anemia, chronic non-spherocytic hemolytic anemia, spontaneous abortion, and neonatal hyperbilirubinemia. Understanding the molecular mechanisms underlying the severity of G6PD deficiency is of great importance but that of many G6PD variants are still unknown. In this study, we report the construction, expression, purification, and biochemical characterization in terms of kinetic properties and stability of five clinical G6PD variants—G6PD Bangkok, G6PD Bangkok noi, G6PD Songklanagarind, G6PD Canton + Bangkok noi, and G6PD Union + Viangchan. G6PD Bangkok and G6PD Canton + Bangkok noi showed a complete loss of catalytic activity and moderate reduction in thermal stability when compared with the native G6PD. G6PD Bangkok noi and G6PD Union + Viangchan showed a significant reduction in catalytic efficiency, whereas G6PD Songklanagarind showed a catalytic activity comparable to the wild-type enzyme. The Union + Viangchan mutation showed a remarkable effect on the global stability of the enzyme. In addition, our results indicate that the location of mutations in G6PD variants affects their catalytic activity, stability, and structure. Hence, our results provide a molecular explanation for clinical manifestations observed in individuals with G6PD deficiency.
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影响因子：
3
作者：
Nantakomol D;Paul R;Palasuwan A;Day NP;White NJ;Imwong M
通讯作者：
Imwong M
DOI：
10.1016/j.bbapap.2007.01.002
发表时间：
2007-03-01
影响因子：
3.2
作者：
Gasymov, Oktay K.;Glasgow, Ben J.
通讯作者：
Glasgow, Ben J.
影响因子：
3.9
作者：
Ainoon, O;Yu, Y H;Hamidah, N H
通讯作者：
Hamidah, N H
影响因子：
4.1
作者：
EGGLESTON, LV;KREBS, HA
通讯作者：
KREBS, HA
影响因子：
5.3
作者：
Iwai, K;Hirono, A;Ishii, A
通讯作者：
Ishii, A