期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 49, 页码 19983-19987出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1214346109
关键词
protein posttranslational modifications; DPH6; diphthine; yeast fitness; P-loop-like motif
资金
- National Institutes of Health/National Institute of General Medical Sciences Grant [GM088276]
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.
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