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5'-deoxy-5'-(3-(3-N,N-dimethylamino)phenoxy)propyl-5'-methyl-5'-thioadenosine + a protein
5'-deoxy-5'-(3-(3-N,N-dimethylamino)phenoxy)propyl-5'-thioadenosine + a methylated protein
-
-
-
-
?
5'-deoxy-5'-(3-phenoxy)propyl-5'-methyl-5'-thioadenosine + a protein
5'-deoxy-5'-(3-phenoxy)propyl-5'-thioadenosine + a methylated protein
-
-
-
-
?
L-histidine-[translation elongation factor 2] + S-adenosyl-L-methionine
2-((3S)-3-amino-3-carboxypropyl)-L-histidine-[translation elongation factor 2] + S-methyl-5'-thioadenosine
L-histidine-[translation elongation factor 2] + [[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl][(2E)-3-carboxyprop-2-en-1-yl]methylsulfonium
2-(3-carboxyprop-2-en-1-yl)-L-histidine-[translation elongation factor 2] + S-methyl-5'-thioadenosine
S-adenosyl-L-methionine analogue, in which the 3-amino-3-carboxypropyl group is replaced with a 3-carboxyallyl group. The analogue is cleaved by Dph2, yielding a paramagnetic (S = 1/2) species, which is assigned to a complex formed between the reaction product, alpha-sulfinyl-3-butenoic acid, and the [4Fe-4S] cluster. Data support a pi-complex between the C=C double bond of alpha-sulfinyl-3-butenoic acid and the unique iron of the [4Fe-4S] cluster, i.e. a radical S-adenosyl-L-methionine-related [4Fe-4S]+ cluster forming an organometallic complex with an alkene
-
-
?
S-adenosyl-L-methionine + L-histidine-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine-[translation elongation factor 2]
S-adenosyl-L-methionine + L-histidine-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-carboxypropyl]-L-histidine-[translation elongation factor 2]
-
-
-
?
S-adenosyl-L-methionine + L-histidine600-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine500-[translation elongation factor 2]
the enzyme is involved in diphthamide biosynthesis
-
-
?
S-adenosyl-L-methionine + L-histidine600-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine600-[translation elongation factor 2]
S-adenosyl-L-methionine + L-histidine699-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine699-[translation elongation factor 2]
the enzyme is involved in diphthamide biosynthesis
-
-
?
S-adenosyl-L-methionine + L-histidine715-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine715-[translation elongation factor 2]
the enzyme is involved in diphthamide biosynthesis
-
-
?
additional information
?
-
-
no activity is detected using dithionite or the Dph3/Cbr1/NADH system as the reductant
-
-
-
L-histidine-[translation elongation factor 2] + S-adenosyl-L-methionine
2-((3S)-3-amino-3-carboxypropyl)-L-histidine-[translation elongation factor 2] + S-methyl-5'-thioadenosine
-
-
-
?
L-histidine-[translation elongation factor 2] + S-adenosyl-L-methionine
2-((3S)-3-amino-3-carboxypropyl)-L-histidine-[translation elongation factor 2] + S-methyl-5'-thioadenosine
-
-
-
?
L-histidine-[translation elongation factor 2] + S-adenosyl-L-methionine
2-((3S)-3-amino-3-carboxypropyl)-L-histidine-[translation elongation factor 2] + S-methyl-5'-thioadenosine
-
-
-
?
S-adenosyl-L-methionine + L-histidine-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine-[translation elongation factor 2]
-
-
-
?
S-adenosyl-L-methionine + L-histidine-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine-[translation elongation factor 2]
-
-
-
?
S-adenosyl-L-methionine + L-histidine-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine-[translation elongation factor 2]
-
-
-
-
?
S-adenosyl-L-methionine + L-histidine-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine-[translation elongation factor 2]
-
-
-
?
S-adenosyl-L-methionine + L-histidine-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine-[translation elongation factor 2]
first step of diphthamide biosynthesis, a unique posttranslational modification on a histidine residue of translational elongation factor 2
-
-
?
S-adenosyl-L-methionine + L-histidine-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine-[translation elongation factor 2]
-
-
-
-
?
S-adenosyl-L-methionine + L-histidine-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine-[translation elongation factor 2]
-
-
-
-
?
S-adenosyl-L-methionine + L-histidine600-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine600-[translation elongation factor 2]
-
-
-
?
S-adenosyl-L-methionine + L-histidine600-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine600-[translation elongation factor 2]
the enzyme is involved in diphthamide biosynthesis
-
-
?
S-adenosyl-L-methionine + L-histidine600-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine600-[translation elongation factor 2]
the 3-amino-3-carboxypropyl radical is added to the imidazole ring in the pathway towards the formation of the product
-
-
?
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5'-deoxy-5'-(3-(3-N,N-dimethylamino)phenoxy)propyl-5'-methyl-5'-thioadenosine + a protein
5'-deoxy-5'-(3-(3-N,N-dimethylamino)phenoxy)propyl-5'-thioadenosine + a methylated protein
-
-
-
-
?
5'-deoxy-5'-(3-phenoxy)propyl-5'-methyl-5'-thioadenosine + a protein
5'-deoxy-5'-(3-phenoxy)propyl-5'-thioadenosine + a methylated protein
-
-
-
-
?
L-histidine-[translation elongation factor 2] + S-adenosyl-L-methionine
2-((3S)-3-amino-3-carboxypropyl)-L-histidine-[translation elongation factor 2] + S-methyl-5'-thioadenosine
S-adenosyl-L-methionine + L-histidine-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine-[translation elongation factor 2]
S-adenosyl-L-methionine + L-histidine-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-carboxypropyl]-L-histidine-[translation elongation factor 2]
-
-
-
?
S-adenosyl-L-methionine + L-histidine600-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine500-[translation elongation factor 2]
the enzyme is involved in diphthamide biosynthesis
-
-
?
S-adenosyl-L-methionine + L-histidine600-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine600-[translation elongation factor 2]
the enzyme is involved in diphthamide biosynthesis
-
-
?
S-adenosyl-L-methionine + L-histidine699-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine699-[translation elongation factor 2]
the enzyme is involved in diphthamide biosynthesis
-
-
?
S-adenosyl-L-methionine + L-histidine715-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine715-[translation elongation factor 2]
the enzyme is involved in diphthamide biosynthesis
-
-
?
L-histidine-[translation elongation factor 2] + S-adenosyl-L-methionine
2-((3S)-3-amino-3-carboxypropyl)-L-histidine-[translation elongation factor 2] + S-methyl-5'-thioadenosine
-
-
-
?
L-histidine-[translation elongation factor 2] + S-adenosyl-L-methionine
2-((3S)-3-amino-3-carboxypropyl)-L-histidine-[translation elongation factor 2] + S-methyl-5'-thioadenosine
-
-
-
?
S-adenosyl-L-methionine + L-histidine-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine-[translation elongation factor 2]
-
-
-
?
S-adenosyl-L-methionine + L-histidine-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine-[translation elongation factor 2]
-
-
-
?
S-adenosyl-L-methionine + L-histidine-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine-[translation elongation factor 2]
-
-
-
-
?
S-adenosyl-L-methionine + L-histidine-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine-[translation elongation factor 2]
first step of diphthamide biosynthesis, a unique posttranslational modification on a histidine residue of translational elongation factor 2
-
-
?
S-adenosyl-L-methionine + L-histidine-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine-[translation elongation factor 2]
-
-
-
-
?
S-adenosyl-L-methionine + L-histidine-[translation elongation factor 2]
S-methyl-5'-thioadenosine + 2-[(3S)-3-amino-3-carboxypropyl]-L-histidine-[translation elongation factor 2]
-
-
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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C259A/C287A
homodimeric mutant enzyme not stable. It is inactive and cannot bind a [4Fe-4S] cluster. Heterodimeric enzyme with a wild-type subunit and a mutant subunit is active
C59A/C287A
inactive mutant lacks the Fe-S cluster. A heterodimer of wild-type subunit and C59A/C287A mutant subunit is stable and active
C106A
-
the mutant shows wild type activity
C128A
-
the mutant shows reduced activity compared to the wild type enzyme
C304A
-
the mutant shows wild type activity
C362A
-
the mutant shows reduced activity compared to the wild type enzyme
C163A
difference in the EPR spectrum of the reduced form, pronounced rhombic main features with greatly increased g-value anisotropy, mutant enzyme is able to transfer the the 3-amino-3-carboxypropyl group onto His600
C163A
mutant enzyme has lower activity than wild-type enzyme and can bind a [4Fe-4S] cluster
C287A
difference in the EPR spectrum, g-tensors are more axial than wild type, mutant enzyme is able to transfer the the 3-amino-3-carboxypropyl group onto His600
C287A
mutant enzyme has lower activity than wild-type enzyme and can bind a [4Fe-4S] cluster
C59A
difference in the EPR spectrum, g-tensors are more axial than wild type, mutant enzyme is able to transfer the the 3-amino-3-carboxypropyl group onto His600
C59A
mutant enzyme has lower activity than wild-type enzyme and can bind a [4Fe-4S] cluster
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Liu, S.; Milne, G.T.; Kuremsky, J.G.; Fink, G.R.; Leppla, S.H.
Identification of the proteins required for biosynthesis of diphthamide, the target of bacterial ADP-ribosylating toxins on translation elongation factor 2
Mol. Cell. Biol.
24
9487-9497
2004
Saccharomyces cerevisiae (P32461), Mus musculus (Q9CR25)
brenda
Zhu, X.; Dzikovski, B.; Su, X.; Torelli, A.; Zhang, Y.; Ealick, S.; Freed, J.; Lin, H.
Mechanistic understanding of Pyrococcus horikoshii Dph2, a [4Fe-4S] enzyme required for diphthamide biosynthesis
Mol. Biosyst.
7
74-81
2011
Pyrococcus horikoshii (O58832), Pyrococcus horikoshii
brenda
Zhang, Y.; Zhu, X.; Torelli, A.T.; Lee, M.; Dzikovski, B.; Koralewski, R.M.; Wang, E.; Freed, J.; Krebs, C.; Ealick, S.E.
Lin, H.: Diphthamide biosynthesis requires an organic radical generated by an iron-sulphur enzyme
Nature
465
891-896
2010
Pyrococcus horikoshii (O58832)
brenda
Mattheakis, L.C.; Sor, F.; Collier, R.J.
Diphthamide synthesis in Saccharomyces cerevisiae: structure of the DPH2 gene
Gene
132
149-154
1993
Saccharomyces cerevisiae (P32461), Saccharomyces cerevisiae FY251 (P32461)
brenda
Webb, T.R.; Cross, S.H.; McKie, L.; Edgar, R.; Vizor, L.; Harrison, J.; Peters, J.; Jackson, I.J.
Diphthamide modification of eEF2 requires a J-domain protein and is essential for normal development
J. Cell Sci.
121
3140-3145
2008
Mus musculus
brenda
Dong, M.; Horitani, M.; Dzikovski, B.; Pandelia, M.E.; Krebs, C.; Freed, J.H.; Hoffman, B.M.; Lin, H.
An organometallic complex formed by an unconventional radical SAM enzyme
J. Am. Chem. Soc.
138
9755-9758
2016
Pyrococcus horikoshii (O58832), Pyrococcus horikoshii
brenda
Abdel-Fattah, W.; Scheidt, V.; Uthman, S.; Stark, M.J.; Schaffrath, R.
Insights into diphthamide, key diphtheria toxin effector
Toxins
5
958-968
2013
Saccharomyces cerevisiae
brenda
Fenwick, M.; Dong, M.; Lin, H.; Ealick, S.
The crystal structure of Dph2 in complex with elongation factor 2 reveals the structural basis for the first step of diphthamide biosynthesis
Biochemistry
58
4343-4351
2019
Methanobrevibacter smithii (A5UMY5), Methanobrevibacter smithii DSM 861 (A5UMY5)
brenda
Dong, M.; Horitani, M.; Dzikovski, B.; Freed, J.; Ealick, S.; Hoffman, B.; Lin, H.
Substrate-dependent cleavage site selection by unconventional radical S-adenosylmethionine enzymes in diphthamide biosynthesis
J. Am. Chem. Soc.
139
5680-5683
2017
Pyrococcus horikoshii
brenda
Dong, M.; Dando, E.; Kotliar, I.; Su, X.; Dzikovski, B.; Freed, J.; Lin, H.
The asymmetric function of Dph1-Dph2 heterodimer in diphthamide biosynthesis
J. Biol. Inorg. Chem.
24
777-782
2019
Saccharomyces cerevisiae
brenda
Dong, M.; Zhang, Y.; Lin, H.
Methods for studying the radical SAM enzymes in diphthamide biosynthesis
Methods Enzymol.
606
421-438
2018
Saccharomyces cerevisiae, Pyrococcus horikoshii, Saccharomyces cerevisiae BY4741
brenda