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Literature summary for 6.3.1.14 extracted from

  • Uthman, S.; Baer, C.; Scheidt, V.; Liu, S.; ten Have, S.; Giorgini, F.; Stark, M.J.; Schaffrath, R.
    The amidation step of diphthamide biosynthesis in yeast requires DPH6, a gene identified through mining the DPH1-DPH5 interaction network (2013), PLoS Genet., 9, e1003334.
    View publication on PubMedView publication on EuropePMC

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + diphthine-[translation elongation factor 2] + NH3 Saccharomyces cerevisiae
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AMP + diphosphate + diphthamide-[translation elongation factor 2]
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?

Organism

Organism UniProt Comment Textmining
Saccharomyces cerevisiae Q12429 gene dph6
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + diphthine-[peptide 686-VNILDVTLHADAIHR-700] + NH3 eEF2-derived peptide sequence Saccharomyces cerevisiae AMP + diphosphate + diphthamide-[peptide 686-VNILDVTLHADAIHR-700]
-
?
ATP + diphthine-[translation elongation factor 2] + NH3
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Saccharomyces cerevisiae AMP + diphosphate + diphthamide-[translation elongation factor 2]
-
?
ATP + diphthine-[translation elongation factor 2] + NH3 modified histidine in eEF2 (His699) is located in the tryptic peptide 686-VNILDVTLHADAIHR-700 Saccharomyces cerevisiae AMP + diphosphate + diphthamide-[translation elongation factor 2]
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?

Synonyms

Synonyms Comment Organism
DPH6
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Saccharomyces cerevisiae
YLR143w
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Saccharomyces cerevisiae

Cofactor

Cofactor Comment Organism Structure
ATP
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Saccharomyces cerevisiae

General Information

General Information Comment Organism
malfunction 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 Saccharomyces cerevisiae
metabolism the enzyme catalyzes the last pathway step, amidation of the intermediate diphthine to diphthamide biosynthesis Saccharomyces cerevisiae
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 Saccharomyces cerevisiae
physiological function 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 Saccharomyces cerevisiae