人类glucose-6-phosphate脱氢酶:晶体结构揭示了一个结构性辅酶ii(+)的分子,并提供洞察酶缺乏症。
文章的细节
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引用
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非盟SW戈夫年代,林VM,亚当斯乔丹
人类glucose-6-phosphate脱氢酶:晶体结构揭示了一个结构性辅酶ii(+)的分子,并提供洞察酶缺乏症。
结构。2000年3月15日,8 (3):293 - 303。
- PubMed ID
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10745013 (在PubMed]
- 文摘
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背景:Glucose-6-phosphate脱氢酶(G6PD)催化作用中的第一个关键步骤磷酸戊糖途径;NADPH的一代这种酶对防止氧化应激至关重要。人类酶二聚体< - - >四聚物平衡及其稳定性取决于辅酶ii(+)的浓度。G6PD缺乏症的结果从许多不同角度x连锁基因的突变编码G6PD和人类酶病是最常见的。严重缺乏会导致慢性non-spherocytic溶血性贫血;常见的症状是新生儿黄疸、蚕豆病和溶血性贫血。结果:我们已经确定的第一个晶体结构人类G6PD(突变广东,Arg459——>亮氨酸)在3一项决议。四聚物的二聚体,二聚体。尽管非常相似的二聚体拓扑中,有两个主要区别的G6PD明串珠菌属mesenteroides:结构性辅酶ii(+)分子,接近二聚体界面但积分单元,是可见的所有子单元的人类酶;和一个intrasubunit二硫化物键i否则无序n端部分。 The few dimer-dimer contacts making the tetramer are charge-charge interactions. CONCLUSIONS: The importance of NADP(+) for stability is explained by the structural NADP(+) site, which is not conserved in prokaryotes. The structure shows that point mutations causing severe deficiency predominate close to the structural NADP(+) and the dimer interface, primarily affecting the stability of the molecule. They also indicate that a stable dimer is essential to retain activity in vivo. As there is an absolute requirement for some G6PD activity, residues essential for coenzyme or substrate binding are rarely modified.