6.3.1.14: diphthine-ammonia ligase
This is an abbreviated version!
For detailed information about diphthine-ammonia ligase, go to the full flat file.
Reaction
Synonyms
Diphthamide synthase, diphthamide synthetase, DPH6, EC 6.3.2.22, Synthetase, diphthamide, YLR143w
ECTree
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General Information
General Information on EC 6.3.1.14 - diphthine-ammonia ligase
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malfunction
metabolism
physiological function
additional information
Dph7, i.e. YBR246w, apparently couples diphthine synthase to diphthine amidation. Dph6 and Dph7 are components required for the amidation step of the diphthamide pathway. In contrast to Dph6, Dph7 may be regulatory. DPH6 and DPH7 are novel sordarin effectors, a feature they share with the diphthamide synthesis genes DPH1-DPH5
failure to synthesize diphthamide affects the accuracy of protein synthesis, DPH6 and DPH7 deletions cause phenotypes typical of bona fide diphthamide mutants, diphthine accumulation in dph6 and dph7 mutants, overview
malfunction
a dph6 deletion strain specifically accumulates the diphthine-modified form of EF2, and shows a failure to complete diphthine amidation resulting in loss of ADP ribosylation acceptor activity of EF2 in the presence of diphtheria toxin in vitro. The amidation defect partially protects against DT in vivo and correlates with resistance to EF2 inactivation and growth inhibition by sordarin, collectively traits typical of bona fide diphthamide synthesis mutants
malfunction
Saccharomyces cerevisiae ATCC 204508 / S288c
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a dph6 deletion strain specifically accumulates the diphthine-modified form of EF2, and shows a failure to complete diphthine amidation resulting in loss of ADP ribosylation acceptor activity of EF2 in the presence of diphtheria toxin in vitro. The amidation defect partially protects against DT in vivo and correlates with resistance to EF2 inactivation and growth inhibition by sordarin, collectively traits typical of bona fide diphthamide synthesis mutants
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the enzyme catalyzes the last pathway step, amidation of the intermediate diphthine to diphthamide biosynthesis
metabolism
diphthamide is formed on eEF-2 only in the presence of both Dph6 and Dph7 enzymes. Enzyme DPH6 catalyzes the last step in the diphthamide synthesis pathway, the amidation of diphthine bound to translation elongation factor 2, while enzyme DPH7 is a methylesterase converting methylated diphthine to diphthine, so that Dph6 can convert it to diphthamide. Diphthamide synthesis pathway, overview
metabolism
the amidation step of diphthamide biosynthesis in yeast requires DPH6, diphthamide synthesis pathway of budding yeast, overview
metabolism
Saccharomyces cerevisiae ATCC 204508 / S288c
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diphthamide is formed on eEF-2 only in the presence of both Dph6 and Dph7 enzymes. Enzyme DPH6 catalyzes the last step in the diphthamide synthesis pathway, the amidation of diphthine bound to translation elongation factor 2, while enzyme DPH7 is a methylesterase converting methylated diphthine to diphthine, so that Dph6 can convert it to diphthamide. Diphthamide synthesis pathway, overview
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metabolism
Saccharomyces cerevisiae ATCC 204508 / S288c
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the amidation step of diphthamide biosynthesis in yeast requires DPH6, diphthamide synthesis pathway of budding yeast, overview
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the enzyme, encoded by gene dph6, catalyzes the biosynthesis of diphthamide, which is a highly modified histidine residue in eukaryal translation elongation factor 2 that is the target for irreversible ADP-ribosylation by diphtheria toxin
physiological function
Dph6 is an ATP-dependent diphthamide synthetase that catalyses the reaction using ammonium as a cofactor. Diphthamide is a highly conserved modification of archaeal and eukaryal translation elongation factor 2. Dph6 is the catalytically relevant amidase in the amidation step of diphthamide synthesis
physiological function
Saccharomyces cerevisiae ATCC 204508 / S288c
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Dph6 is an ATP-dependent diphthamide synthetase that catalyses the reaction using ammonium as a cofactor. Diphthamide is a highly conserved modification of archaeal and eukaryal translation elongation factor 2. Dph6 is the catalytically relevant amidase in the amidation step of diphthamide synthesis
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