An aminoacyl-tRNA synthetase paralog with a catalytic role in histidine biosynthesis
An aminoacyl-tRNA synthetase paralog with a catalytic role in histidine biosynthesis
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DOI：
10.1073/pnas.96.16.8985
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发表时间：
1999-08-03
影响因子：
11.1
通讯作者：
Francklyn, C
中科院分区：
文献类型：
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作者：
Sissler, M;Delorme, C;Francklyn, C
除了在蛋白质生物合成中的重要催化作用外，氨酰-tRNA 合成酶还参与许多其他功能，包括通过转酰胺基途径调节基因表达和氨基酸生物合成。在此，我们描述了一类氨酰基-tRNA合成酶样（HisZ）蛋白，其基于当代II类组氨酰基-tRNA合成酶的催化核心，其成员缺乏氨酰化活性，但却是组氨酸生物合成ATP磷酸核糖基转移酶（HisG）中第一个酶的重要组成部分。比较基因组学有助于预测乳酸乳球菌中HisZ的功能，该技术揭示了存在之间的联系或者 HisZ 的缺失以及 HisG 多肽长度的系统变异。 HisZ 是组氨酸原养型所必需的，另外三个证据支持 HisZ 直接参与转移酶功能。 (i) 遗传实验表明，大肠杆菌（不具有 HisZ）中 HisG 的框内缺失的互补需要乳酸乳球菌中的 HisG 和 HisZ，(ii) 亲和层析过程中 HisG 和 HisZ 的共洗脱提供了直接物理相互作用的证据。 (iii) HisG 和 HisZ 都是催化 ATP 磷酸核糖基转移酶反应所必需的。对连接氨基酸生物合成和蛋白质合成的共同蛋白质结构域的观察意味着氨基酸生物合成和蛋白质之间的早期联系。
In addition to their essential catalytic role in protein biosynthesis, aminoacyl-tRNA synthetases participate in numerous other functions, including regulation of gene expression and amino acid biosynthesis via transamidation pathways. Herein, we describe a class of aminoacyl-tRNA synthetase-like (HisZ) proteins based on the catalytic core of the contemporary class II histidyl-tRNA synthetase whose members lack aminoacylation activity but are instead essential components of the first enzyme in histidine biosynthesis ATP phosphoribosyltransferase (HisG), Prediction of the function of HisZ in Lactococcus lactis was assisted by comparative genomics, a technique that revealed a link between the presence or the absence of HisZ and a systematic variation in the length of the HisG polypeptide. HisZ is required for histidine prototrophy, and three other lines of evidence support the direct involvement of HisZ in the transferase function. (i) Genetic experiments demonstrate that complementation of an in-frame deletion of HisG from Escherichia coli (which does not possess HisZ) requires both HisG and HisZ from L. lactis, (ii) Coelution of HisG and HisZ during affinity chromatography provides evidence of direct physical interaction. (iii) Both HisG and HisZ are required for catalysis of the ATP phosphoribosyltransferase reaction. This observation of a common protein domain linking amino acid biosynthesis and protein synthesis implies an early connection between the biosynthesis bf amino acids and proteins.