Identification of a single nucleotide change in the hypoxanthine-guanine phosphoribosyltransferase gene (HPRTYale) responsible for Lesch-Nyhan syndrome.
Identification of a single nucleotide change in the hypoxanthine-guanine phosphoribosyltransferase gene (HPRTYale) responsible for Lesch-Nyhan syndrome.
复制标题
鉴定导致 Lesch-Nyhan 综合征的次黄嘌呤鸟嘌呤磷酸核糖基转移酶基因 (HPRTYale) 中的单核苷酸变化。
DOI：
10.1172/jci113846
复制
发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Palella,TD
中科院分区：
文献类型：
--
作者：
Fujimori,S;Davidson,BL;Kelley,WN;Palella,TD
次黄嘌呤-鸟嘌呤磷酸核糖转移酶（HPRT）的完全缺乏导致Lesch-Nyhan综合征。先前对来自Lesch-Nyhan综合征受试者的HPRT突变形式HPRTYale的表征显示正常的mRNA和蛋白质浓度，没有残留的催化活性，并且在PAGE时阴极迁移。我们克隆了HPRTYale cDNA并进行了序列测定。全长HPRTYale cDNA的核苷酸序列显示与正常HPRT cDNA相比，在核苷酸位置211处有一个单核苷酸取代：G-C。这种颠换预测精氨酸取代甘氨酸的氨基酸位置71，解释了HPRTYale的阴极迁移。Chou-Fasman二级结构分析预测在含有突变的区域中β-转角形成的概率的变化。包含大体积精氨酸侧链代替甘氨酸可能也会破坏蛋白质折叠。克隆突变形式的cDNA可以识别特定的突变，提供对突变机制的洞察，并促进突变蛋白的结构-功能分析。图片
Complete deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) causes the Lesch-Nyhan syndrome. Previous characterization of a mutant form of HPRT, HPRTYale, from a subject with the Lesch-Nyhan syndrome revealed normal mRNA and protein concentrations, no residual catalytic activity, and cathodal migration upon PAGE. We have cloned and sequenced HPRTYale cDNA. The nucleotide sequence of full-length HPRTYale cDNA revealed a single nucleotide substitution compared with normal HPRT cDNA: G----C at nucleotide position 211. This transversion predicts substitution of arginine for glycine at amino acid position 71, explaining the cathodal migration of HPRTYale. Chou-Fasman secondary structure analysis predicts a change in the probability of beta-turn formation in the region containing the mutation. Inclusion of the bulky arginine side chain in place of glycine probably disrupts protein folding as well. Cloning mutant forms of cDNA allows identification of specific mutations, provides insight into mutational mechanisms, and facilitates structure-function analysis of mutant proteins.Images