Diphthamide

Diphthamide is a post-translationally modified histidine amino acid found in archaeal and eukaryotic elongation factor 2 (eEF-2).

Diphthamide

Names
IUPAC name 2-Amino-3-[2-(3-carbamoyl-3-trimethylammonio-propyl)-3H-imidazol-4-yl]propanoate
Identifiers
CAS Number	75645-22-6 Y
3D model (JSmol)	Interactive image Interactive image
ChemSpider	4942856 Y
PubChem CID	6438375
UNII	86L3ZZ4408 Y
CompTox Dashboard (EPA)	DTXSID60904010
InChI 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
SMILES 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
Chemical formula	C13H23N5O3
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). Y verify (what is YN ?) Infobox references

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-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).^[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]