Human hypoxanthine (guanine) phosphoribosyltransferase: an amino acid substitution in a mutant form of the enzyme isolated from a patient with gout.
Human hypoxanthine (guanine) phosphoribosyltransferase: an amino acid substitution in a mutant form of the enzyme isolated from a patient with gout.
复制标题
人次黄嘌呤（鸟嘌呤）磷酸核糖基转移酶：从痛风患者中分离出的酶的突变形式的氨基酸取代。
DOI：
10.1073/pnas.80.3.870
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发表时间：
1983
影响因子：
11.1
通讯作者：
Kelley,WN
中科院分区：
文献类型：
--
作者：
Wilson,JM;Tarr,GE;Kelley,WN
我们研究了一名严重痛风患者次黄嘌呤（鸟嘌呤）磷酸核糖转移酶（HPRT；IMP：焦磷酸磷酸核糖转移酶，EC 2.4.2.8）缺乏的分子基础。我们在之前的研究中报道了从该患者的红细胞和培养的淋巴母细胞中分离出 HPRT 的独特结构变异体。这种酶变体被称为 HPRTLondon，其特点是红细胞和淋巴母细胞中 HPRT 蛋白浓度降低、Vmax 正常、次黄嘌呤 Km 增加 5 倍、等电点正常以及亚基分子量明显较小。比较肽图谱实验揭示了 HPRTLondon 中的单个异常胰蛋白酶肽。来自 HPRTLondon 的异常肽的 Edman 降解鉴定出 109 位的丝氨酸至亮氨酸氨基酸替换。这种替换可以通过丝氨酸 109 密码子中的单核苷酸变化来解释（UCA 导致 UUA）。因此，HPRT 基因座的突变现已在分子水平上得到定义。
We have investigated the molecular basis for a deficiency of the enzyme hypoxanthine (guanine) phosphoribosyltransferase (HPRT; IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) in a patient with a severe form of gout. We reported in previous studies the isolation of a unique structural variant of HPRT from this patient's erythrocytes and cultured lymphoblasts. This enzyme variant, which is called HPRTLondon, is characterized by a decreased concentration of HPRT protein in erythrocytes and lymphoblasts, a normal Vmax, a 5-fold increased Km for hypoxanthine, a normal isoelectric point, and an apparently smaller subunit molecular weight. Comparative peptide mapping experiments revealed a single abnormal tryptic peptide in HPRTLondon. Edman degradation of the aberrant peptide from HPRTLondon identified a serine-to-leucine amino acid substitution at position 109. This substitution can be explained by a single nucleotide change in the codon for serine-109 (UCA leads to UUA). Thus a mutation at the HPRT locus has now been defined at the molecular level.