ASPARTYLGLUCOSAMINURIA - CDNA-ENCODING HUMAN ASPARTYLGLUCOSAMINIDASE AND THE MISSENSE MUTATION CAUSING THE DISEASE
ASPARTYLGLUCOSAMINURIA - CDNA-ENCODING HUMAN ASPARTYLGLUCOSAMINIDASE AND THE MISSENSE MUTATION CAUSING THE DISEASE
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DOI：
10.1002/j.1460-2075.1991.tb07920.x
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发表时间：
1991-01-01
期刊：
影响因子：
11.4
通讯作者：
PELTONEN, L
中科院分区：
文献类型：
--
作者：
IKONEN, E;BAUMANN, M;PELTONEN, L
我们分离了一个2.1kb的cDNA，它编码人氨基葡萄糖苷酶（阿加，E.C. 3.5.1.26）上提供。 这种溶酶体酶的活性在乙酰氨基葡萄糖尿症（AGU）中缺乏，AGU是一种导致严重智力迟钝的遗传性溶酶体蓄积疾病。 由阿加cDNA推导的多肽链由346个氨基酸组成，具有两个潜在的N-糖基化位点和11个半胱氨酸残基。 该cDNA在COS-1细胞中的瞬时表达导致免疫沉淀阿加蛋白的表达增加。 从AGU患者扩增的阿加cDNA的直接测序揭示了G -> C转换，导致半胱氨酸163被丝氨酸取代。 该突变随后在所有20名分析的芬兰AGU患者中发现，在所有53名携带者中以杂合形式存在，而在67名对照个体中没有发现，这表明它代表了在该孤立人群中富集的主要AGU引起突变。 由于该突变导致预测的阿加多肽链的柔性发生变化，并去除了分子内的S-S桥，因此很可能解释了AGU患者细胞和组织中发现的酶活性缺陷。
We have isolated a 2.1 kb cDNA which encodes human aspartylglucosaminidase (AGA, E.C. 3.5.1.26). The activity of this lysosomal enzyme is deficient in aspartylglucosaminuria (AGU), a recessively inherited lysosomal accumulation disease resulting in severe mental retardation. The polypeptide chain deduced from the AGA cDNA consists of 346 amino acids, has two potential N-glycosylation sites and 11 cysteine residues. Transient expression of this cDNA in COS-1 cells resulted in increased expression of immunoprecipitable AGA protein. Direct sequencing of amplified AGA cDNA from an AGU patient revealed a G --> C transition resulting in the substitution of cysteine 163 with serine. This mutation was subsequently found in all the 20 analyzed Finnish AGU patients, in the heterozygous form in all 53 carriers and in none of 67 control individuals, suggesting that it represents the major AGU causing mutation enriched in this isolated population. Since the mutation produces a change in the predicted flexibility of the AGA polypeptide chain and removes an intramolecular S-S bridge, it most probably explains the deficient enzyme activity found in cells and tissues of AGU patients.