Chemogenomic approach identified yeast YLR143W as diphthamide synthetase
Chemogenomic approach identified yeast YLR143W as diphthamide synthetase
复制标题
DOI：
10.1073/pnas.1214346109
复制
发表时间：
2012-12-04
影响因子：
11.1
通讯作者：
Lin, Hening
中科院分区：
文献类型：
--
作者：
Su, Xiaoyang;Lin, Zhewang;Lin, Hening
在任何已测序的基因组中，许多基因的功能都是未知的。化学和遗传扰动的组合已被用于研究基因功能。在这里，我们提出了一个案例，这种“化学基因组学”的信息可以有效地用于确定丢失的基因在一个定义的生物途径。特别是，我们确定了以前未知的酶的联苯二酰胺合成酶的最后一步的联苯二酰胺生物合成。我们发现酵母蛋白YLR 143W是催化使用铵和ATP的最后酰胺化步骤的联苯二酰胺合成酶。邻苯二甲酰胺合成酶在真核生物中是进化保守的。先前未表征的人类基因ATPBD4是酵母YLR 143 W的直系同源物，并且完全挽救了酵母中YLR 143 W的缺失。
Many genes are of unknown functions in any sequenced genome. A combination of chemical and genetic perturbations has been used to investigate gene functions. Here we present a case that such "chemogenomics" information can be effectively used to identify missing genes in a defined biological pathway. In particular, we identified the previously unknown enzyme diphthamide synthetase for the last step of diphthamide biosynthesis. We found that yeast protein YLR143W is the diphthamide synthetase catalyzing the last amidation step using ammonium and ATP. Diphthamide synthetase is evolutionarily conserved in eukaryotes. The previously uncharacterized human gene ATPBD4 is the ortholog of yeast YLR143W and fully rescues the deletion of YLR143W in yeast.