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{{chembox| Watchedfields = changed| verifiedrevid = 428011922| ImageFile = diphthamide.png| ImageSize = 200px| IUPACName = 2-Amino-3-[2-(3-carbamoyl-3-trimethylammonio-propyl)-3H-imidazol-4-yl]propanoate| OtherNames = |Section1={{Chembox Identifiers

correct|chemspider}}| ChemSpiderID = 4942856| 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)| InChIKey = FOOBQHKMWYGHCE-UHFFFAOYAN| SMILES1 = [O-]C(=O)C(N)Cc1cnc([nH]1)CCC(C(=O)N)[N+](C)(C)C

correct|chemspider}}| StdInChI = 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)

correct|chemspider}}| StdInChIKey = FOOBQHKMWYGHCE-UHFFFAOYSA-N

correct|CAS}}| CASNo = 75645-22-6

correct|FDA}}| UNII = 86L3ZZ4408| PubChem = 6438375| SMILES = C[N+](C)(C)C(CCC1=NC=C(N1)CC(C(=O)[O-])N)C(=O)N }}|Section2={{Chembox Properties

H=23

O=3| MolarMass = 297.354 g/mol| Appearance = | Density = | MeltingPt = | BoilingPt = | Solubility = }}

MainHazards = | FlashPt = | AutoignitionPt = {edih} }}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. Besides this toxin, it is also targeted by exotoxin A from Pseudomonas aeruginosa.JOURNAL, Liu S, Wiggins JF, Sreenath T, Kulkarni AB, Ward JM, Leppla SH, Dph3, a small protein required for diphthamide biosynthesis, is essential in mouse development, Molecular and Cellular Biology, 26, 10, 3835–3841, May 2006, 16648478, 1488998, 10.1128/MCB.26.10.3835-3841.2006, It is the only target of these toxins. 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.JOURNAL, Jørgensen R, Merrill AR, Andersen GR, The life and death of translation elongation factor 2, Biochemical Society Transactions, 34, Pt 1, 1–6, February 2006, 16246167, 10.1042/BST20060001, Diphthamide is biosynthesized from histidine and S-adenosyl methionine (SAM). The side chain bound to imidazole group and all methyl groups come from SAM. The whole synthesis takes place in three steps: 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). Biological function Diphthamide ensures translation fidelity.JOURNAL, Su X, Lin Z, Lin H, The biosynthesis and biological function of diphthamide, Critical Reviews in Biochemistry and Molecular Biology, 48, 6, 515–521, 2013-11-01, 23971743, 4280834, 10.3109/10409238.2013.831023, The presence or absence of diphthamide is known to affect NF-κB or death receptor pathways.JOURNAL, Stahl S, da Silva Mateus Seidl AR, Ducret A, Kux van Geijtenbeek S, Michel S, Racek T, Birzele F, Haas AK, Rueger R, Gerg M, Niederfellner G, Pastan I, Brinkmann U, 6, 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, August 2015, 26261303, 4553792, 10.1073/pnas.1512863112, free, 2015PNAS..11210732S, References {{Reflist}}