同型半胱氨酸尿中突变胱氨酸-合成酶亚基血红素结合和聚集受损。

文章的细节

引用

Janosik M, oliverusova J, Janosikova B, Sokolova J, Kraus E, Kraus JP, Kozich V

同型半胱氨酸尿中突变胱氨酸-合成酶亚基血红素结合和聚集受损。

胡恩杰。2001年6月;68(6):1506-13。Epub 2001 5月15日。

PubMed ID
11359213 (PubMed视图
摘要

在过去的20年里,在前捷克斯洛伐克检测到胱氨酸β -合成酶(CBS)缺乏症,计算频率为1:349 000。临床表现为典型的同型半胱氨酸尿,21例患者中约半数对吡哆醇无反应。在30个独立的同型半胱氨酸等位基因中检测到12个不同的突变。一半的等位基因携带c.833T—>C或IVS11-2A—>C突变;其余的等位基因包含私有突变。采用PCR-RFLP分析了5个过早终止密码子突变mrna的丰度。两条mrna c.828_931ins104 (IVS7+1G—>A)和c.1226G—>a,由于无义介导的衰变,在细胞质中严重减少。相比之下,其他三种mrna -c。19_20insC, c.28_29delG, and c.210_235del26 (IVS1-1G-->C)-were stable. Native western blot analysis of 14 mutant fibroblast lines showed a paucity of CBS antigen, which was detectable only in aggregates. Five mutations-A114V (c.341C-->T), A155T (c.463G-->A), E176K (c.526G-->A), I278T (c.833T-->C), and W409_G453del (IVS11-2A-->C)-were expressed in Escherichia coli. All five mutant proteins formed substantially more aggregates than did the wild-type CBS, and no aggregates contained heme. These data suggest that abnormal folding, impaired heme binding, and aggregation of mutant CBS polypeptides may be common pathogenic mechanisms in CBS deficiency.

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的名字 UniProt ID
胱硫醚beta-synthase P35520 细节