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Diphthamide
Names
IUPAC name
2-Amino-3-[2-(3-carbamoyl-3-trimethylammonio-propyl)-3H -imidazol-4-yl]propanoate
Identifiers
ChemSpider
UNII
InChI=1S/C13H23N5O3/c1-18(2,3)10(12(15)19)4-5-11-16-7-8(17-11)6-9(14)13(20)21/h7,9-10H,4-6,14H2,1-3H3,(H3-,15,16,17,19,20,21)
Y Key: FOOBQHKMWYGHCE-UHFFFAOYSA-N
Y InChI=1/C13H23N5O3/c1-18(2,3)10(12(15)19)4-5-11-16-7-8(17-11)6-9(14)13(20)21/h7,9-10H,4-6,14H2,1-3H3,(H3-,15,16,17,19,20,21)
Key: FOOBQHKMWYGHCE-UHFFFAOYAN
C[N+](C)(C)C(CCC1=NC=C(N1)CC(C(=O)[O-])N)C(=O)N
[O-]C(=O)C(N)Cc1cnc([nH]1)CCC(C(=O)N)[N+](C)(C)C
Properties
C 13 H 23 N 5 O 3
Molar mass
297.354 g/mol
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
Chemical compound
Diphthamide is a post-translationally modified
histidine
amino acid found in archaeal and
eukaryotic elongation factor 2 (eEF-2).
Dipthamide is named after the toxin produced by the bacterium
Corynebacterium diphtheriae , which targets diphthamide.
[1] Besides this toxin, it is also targeted by
exotoxin A from
Pseudomonas aeruginosa .
[1]
[2] It is the only target of these toxins.
[2]
Structure and biosynthesis
Diphthamide is proposed to be a 2-[3-carboxyamido-3-(trimethylammonio)propyl]histidine. Though this structure has been confirmed by
X-ray crystallography , its stereochemistry is uncertain.
[1]
[3]
Diphthamide is biosynthesized from histidine and
S -adenosyl methionine (SAM).
[1] The side chain bound to
imidazole group and all
methyl groups come from SAM. The whole synthesis takes place in three steps:
[1]
transfer of 3-amino-3-carboxylpropyl group from SAM
transfer of three methyl groups from SAM – synthesis of
diphtine
amidation – synthesis of diphthamide
In eukaryotes, this biosynthetic pathway contains a total of 7 genes (Dph1-7).
[1]
Biological function
Diphthamide ensures
translation fidelity.
[1]
The presence or absence of diphthamide is known to affect
NF-κB or death receptor pathways.
[4]
References
^
a
b
c
d
e
f
g Su X, Lin Z, Lin H (2013-11-01).
"The biosynthesis and biological function of diphthamide" . Critical Reviews in Biochemistry and Molecular Biology . 48 (6): 515–521.
doi :
10.3109/10409238.2013.831023 .
PMC
4280834 .
PMID
23971743 .
^
a
b Liu S, Wiggins JF, Sreenath T, Kulkarni AB, Ward JM, Leppla SH (May 2006).
"Dph3, a small protein required for diphthamide biosynthesis, is essential in mouse development" . Molecular and Cellular Biology . 26 (10): 3835–3841.
doi :
10.1128/MCB.26.10.3835-3841.2006 .
PMC
1488998 .
PMID
16648478 .
^ Jørgensen R, Merrill AR, Andersen GR (February 2006). "The life and death of translation elongation factor 2". Biochemical Society Transactions . 34 (Pt 1): 1–6.
doi :
10.1042/BST20060001 .
PMID
16246167 .
^ Stahl S, da Silva Mateus Seidl AR, Ducret A, Kux van Geijtenbeek S, Michel S, Racek T, et al. (August 2015).
"Loss of diphthamide pre-activates NF-κB and death receptor pathways and renders MCF7 cells hypersensitive to tumor necrosis factor" . Proceedings of the National Academy of Sciences of the United States of America . 112 (34): 10732–10737.
Bibcode :
2015PNAS..11210732S .
doi :
10.1073/pnas.1512863112 .
PMC
4553792 .
PMID
26261303 .