Biochemical and structural insights into an allelic variant causing the lysosomal storage disorder - aspartylglucosaminuria.
Biochemical and structural insights into an allelic variant causing the lysosomal storage disorder - aspartylglucosaminuria.
复制标题
对引起溶酶体贮积症的等位基因变异 - 天冬氨葡萄糖胺尿症的生化和结构见解。
DOI：
10.1002/1873-3468.13190
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发表时间：
2018
期刊：
影响因子：
3.5
通讯作者：
Guo,Hwai-Chen
中科院分区：
文献类型：
--
作者：
Pande,Suchita;Bizilj,William;Guo,Hwai-Chen
天冬氨酰葡糖胺尿症（AGU）是一种由糖基天冬酰胺酶（GA）水解酶缺陷引起的溶酶体储存障碍。以前，我们表明，加拿大AGU突变破坏了强制性的分子内自动加工与酶作为一个无活性的前体被困。在这里，我们报告的生化和结构表征的模型酶对应于芬兰AGU等位基因，T234 I变异。与加拿大对应物不同，芬兰变体能够缓慢自动处理以产生GA天然底物的可检测水解活性。我们已经确定了芬兰AGU模型的1.6 π-分辨率结构，并建立了一个酶-底物复合物，为分析点突变对成熟酶的KMandkcat的负面影响提供了结构基础。酶糖基天冬酰胺酶或乙酰氨基葡萄糖苷酶，EC 3.5.1.26。
Aspartylglucosaminuria (AGU) is a lysosomal storage disorder caused by defects of the hydrolase glycosylasparaginase (GA). Previously, we showed that a Canadian AGU mutation disrupts an obligatory intramolecular autoprocessing with the enzyme trapped as an inactive precursor. Here, we report biochemical and structural characterizations of a model enzyme corresponding to a Finnish AGU allele, the T234I variant. Unlike the Canadian counterpart, the Finnish variant is capable of a slow autoprocessing to generate detectible hydrolyzation activity of the natural substrate of GA. We have determined a 1.6 Å‐resolution structure of the Finnish AGU model and built an enzyme–substrate complex to provide a structural basis for analyzing the negative effects of the point mutation onKMandkcatof the mature enzyme.EnzymeGlycosylasparaginase or aspartylglucosaminidase, EC3.5.1.26.