Diphthamide

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title: "Diphthamide" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["amino-acids", "imidazoles", "quaternary-ammonium-compounds", "post-translational-modification", "zwitterions"] topic_path: "general/amino-acids" source: "https://en.wikipedia.org/wiki/Diphthamide" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

| 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 | ChemSpiderID_Ref = | 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 | StdInChI_Ref = | 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) | StdInChIKey_Ref = | StdInChIKey = FOOBQHKMWYGHCE-UHFFFAOYSA-N | CASNo_Ref = | CASNo = 75645-22-6 | UNII_Ref = | UNII = 86L3ZZ4408 | PubChem = 6438375 | SMILES = CN+(C)C(CCC1=NC=C(N1)CC(C(=O)[O-])N)C(=O)N |Section2={{Chembox Properties | C=13 | H=23 | N=5 | O=3 | MolarMass = 297.354 g/mol | Appearance = | Density = | MeltingPt = | BoilingPt = | Solubility = |Section3={{Chembox Hazards | MainHazards = | FlashPt = | AutoignitionPt =

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. 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.

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-carboxypropyl 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.

The presence or absence of diphthamide is known to affect NF-κB or death receptor pathways.

References

References

  1. (May 2006). "Dph3, a small protein required for diphthamide biosynthesis, is essential in mouse development". Molecular and Cellular Biology.
  2. (February 2006). "The life and death of translation elongation factor 2". Biochemical Society Transactions.
  3. (2013-11-01). "The biosynthesis and biological function of diphthamide". Critical Reviews in Biochemistry and Molecular Biology.
  4. (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.

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amino-acidsimidazolesquaternary-ammonium-compoundspost-translational-modificationzwitterions