Ishii S, Kase R, Sakuraba H, Suzuki Y
Department of Clinical Genetics, Tokyo Metropolitan Institute of Medical Science, Japan.
Biochem Biophys Res Commun. 1993 Dec 30;197(3):1585-9. doi: 10.1006/bbrc.1993.2659.
The expression product of a mutant alpha-galactosidase gene, Q279E (279Gln-->Glu), found in an atypical variant (cardiac form) of Fabry disease, was purified and characterized. It had kinetic properties similar to those of normal alpha-galactosidase, but was markedly thermolabile at neutral pH. Galactose and melibiose at high concentrations stabilized the mutant enzyme in vitro. Its catalytic activity was 15% of that for the normal enzyme, when it was expressed in COS-1 cells at 37 degrees C. The activity increased at 30 degrees C or in the presence of galactose at 37 degrees C. An increase was also observed in lymphoblasts from a patient with this mutation in the presence of galactose or melibiose. We conclude that this mutant protein is posttranslationally inactivated under the neutral conditions in the cells. The possibility of a new therapeutic approach is suggested.
在法布里病的一种非典型变体（心脏型）中发现的突变α-半乳糖苷酶基因Q279E（279Gln→Glu）的表达产物被纯化并进行了表征。它具有与正常α-半乳糖苷酶相似的动力学特性，但在中性pH下明显不耐热。高浓度的半乳糖和蜜二糖在体外可稳定突变酶。当它在COS-1细胞中于37℃表达时，其催化活性为正常酶的15%。在30℃或在37℃存在半乳糖的情况下活性增加。在存在半乳糖或蜜二糖的情况下，来自该突变患者的淋巴母细胞中也观察到活性增加。我们得出结论，这种突变蛋白在细胞内的中性条件下在翻译后失活。这提示了一种新的治疗方法的可能性。
