A threonine synthase homolog from a mammalian genome
A threonine synthase homolog from a mammalian genome
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DOI：
10.1016/j.bbrc.2006.09.112
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发表时间：
2006-12-01
影响因子：
3.1
通讯作者：
Peracchi, Alessio
中科院分区：
文献类型：
--
作者：
Donini, Stefano;Percudani, Riccardo;Peracchi, Alessio
一些脊椎动物的基因组含有两个编码与苏氨酸合酶 (TS) 高度相似的蛋白质的基因，尽管 L-苏氨酸 (L-Thr) 的生物合成尚不清楚在这些动物中发生。我们报告了两种 TS 样基因、一种鼠类 TS 同源物 (mTSH2) 的重组表达及其初始生化特征的生物信息学分析。重组mTSH2含有结合的5'-磷酸吡哆醛(PLP)，但不合成L-Thr。然而，该酶确实结合了 O-磷酸高丝氨酸（PHS；实际的 TS 底物）并将其降解为 α-酮丁酸、磷酸盐和氨——这是微生物 TS 的已知副反应。 mTSH2 还将 O-磷酸苏氨酸 (PThr) 降解为 α-酮丁酸，表明它可以作为 γ- 和 P- 磷酸化底物的分解代谢磷酸裂解酶。这些发现表明 mTSH2 具有不寻常的进化起源，即在后生动物中，原始 TS 酶在 L-Thr 生物合成途径被解除后“再循环”为磷酸裂合酶。 (c) 2006 Elsevier Inc. 保留所有权利。
The genomes of several vertebrates contain two genes encoding proteins highly similar to threonine synthase (TS), even though the biosynthesis Of L-threonine (L-Thr) is not known to occur in these animals. We report a bioinformatic analysis of the two TS-like genes, the recombinant expression of one murine TS homolog (mTSH2) and its initial biochemical characterization. Recombinant mTSH2 contained bound pyridoxal-5'-phosphate (PLP), but did not synthesize L-Thr. The enzyme did, however, bind O-phospho-homoserine (PHS; the actual TS substrate) and degraded it to alpha-ketobutyrate, phosphate, and ammonia-a known side reaction of microbial TSs. mTSH2 also degraded O-phospho-threonine (PThr) to alpha-ketobutyrate, showing that it can act as a catabolic phospho-lyase on both gamma- and P-phosphorylated substrates. These findings suggest an unusual evolutionary origin for mTSH2, whereby an original TS enzyme became 'recycled' into a phospho-lyase upon dismissal, in metazoa, of the L-Thr biosynthetic pathway. (c) 2006 Elsevier Inc. All rights reserved.