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Chemogenomic approach identified yeast YLR143W as diphthamide synthetase.

ABSTRACT: 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.

SUBMITTER: Su X

PROVIDER: S-EPMC3523822 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Chemogenomic approach identified yeast YLR143W as diphthamide synthetase.

Su Xiaoyang X Lin Zhewang Z Chen Wei W Jiang Hong H Zhang Sheng S Lin Hening H

Proceedings of the National Academy of Sciences of the United States of America 20121119 49

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 cat ...[more]

PMID: 23169644

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