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Information on EC 6.3.1.14 - diphthine-ammonia ligase and Organism(s) Saccharomyces cerevisiae and UniProt Accession Q12429

for references in articles please use BRENDA:EC6.3.1.14
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IUBMB Comments
This amidase catalyses the last step in the conversion of an L-histidine residue in the translation elongation factor EF2 to diphthamide. This factor is found in all archaea and eukaryota, but not in eubacteria, and is the target of bacterial toxins such as the diphtheria toxin and the Pseudomonas exotoxin A (see EC 2.4.2.36, NAD+---diphthamide ADP-ribosyltransferase). The substrate of the enzyme, diphthine, is produced by EC 2.1.1.98, diphthine synthase.
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Saccharomyces cerevisiae
UNIPROT: Q12429
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The taxonomic range for the selected organisms is: Saccharomyces cerevisiae
The expected taxonomic range for this enzyme is: Eukaryota, Archaea, Bacteria
Synonyms
ylr143w, diphthamide synthetase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diphthamide synthetase
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Diphthamide synthase
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Synthetase, diphthamide
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
peptide synthase reaction
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PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
diphthine-[translation elongation factor 2]:ammonia ligase (AMP-forming)
This amidase catalyses the last step in the conversion of an L-histidine residue in the translation elongation factor EF2 to diphthamide. This factor is found in all archaea and eukaryota, but not in eubacteria, and is the target of bacterial toxins such as the diphtheria toxin and the Pseudomonas exotoxin A (see EC 2.4.2.36, NAD+---diphthamide ADP-ribosyltransferase). The substrate of the enzyme, diphthine, is produced by EC 2.1.1.98, diphthine synthase.
CAS REGISTRY NUMBER
COMMENTARY hide
114514-33-9
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + diphthine-[peptide 686-VNILDVTLHADAIHR-700] + NH3
AMP + diphosphate + diphthamide-[peptide 686-VNILDVTLHADAIHR-700]
show the reaction diagram
eEF2-derived peptide sequence
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?
ATP + diphthine-[translation elongation factor 2] + NH3
AMP + diphosphate + diphthamide-[translation elongation factor 2]
show the reaction diagram
additional information
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the repurified DELTAdph7 eEF-2 is a substrate for the amidation by Dph6 alone. In contrast, FLAG-tagged DELTAdph7 eEF-2 incubated without Dph7 does not form diphthamide
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + diphthine-[translation elongation factor 2] + NH3
AMP + diphosphate + diphthamide-[translation elongation factor 2]
show the reaction diagram
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
construction of a dph6 gene knockout mutant strain
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene DPH6, the gene is identified through mining the DPH1-DPH5 interaction network
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
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
PLoS Genet.
9
e1003334
2013
Saccharomyces cerevisiae (Q12429)
Manually annotated by BRENDA team
Lin, Z.; Su, X.; Chen, W.; Ci, B.; Zhang, S.; Lin, H.
Dph7 catalyzes a previously unknown demethylation step in diphthamide biosynthesis
J. Am. Chem. Soc.
136
6179-6182
2014
Saccharomyces cerevisiae (Q12429), Saccharomyces cerevisiae ATCC 204508 / S288c (Q12429)
Manually annotated by BRENDA team
Schaffrath, R.; Stark, M.J.
Decoding the biosynthesis and function of diphthamide, an enigmatic modification of translation elongation factor 2 (EF2)
Microb. Cell
1
203-205
2014
Saccharomyces cerevisiae (Q12429), Saccharomyces cerevisiae ATCC 204508 / S288c (Q12429)
Manually annotated by BRENDA team