Diphthamide: Difference between revisions

| Watchedfields = changed

| verifiedrevid = 428011922

| IUPACName = 2-Amino-3-[2-(3-carbamoyl-3-trimethylammonio-propyl)-3''H''-imidazol-4-yl]propanoate

|Section1={{Chembox Identifiers

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| SMILES1 = [O-]C(=O)C(N)Cc1cnc([nH]1)CCC(C(=O)N)[N+](C)(C)C

| CASNo_Ref = {{cascite|correct|CAS}}

| UNII_Ref = {{fdacite|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

| 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 [[EEF2|eukaryotic elongation factor 2]] (eEF-2).

Dipthamide is named after the toxin produced by the bacterium ''[[Corynebacterium diphtheriae]]'', which targets diphthamide.<ref name="pmc4280834" /> Besides this toxin, it is also targeted by [[exotoxin A]] from ''[[Pseudomonas aeruginosa]]''.<ref name="pmc4280834" /><ref name=":2">{{cite journal | vauthors = Liu S, Wiggins JF, Sreenath T, Kulkarni AB, Ward JM, Leppla SH | title = Dph3, a small protein required for diphthamide biosynthesis, is essential in mouse development | journal = Molecular and Cellular Biology | volume = 26 | issue = 10 | pages = 3835–3841 | date = May 2006 | pmid = 16648478 | pmc = 1488998 | doi = 10.1128/MCB.26.10.3835-3841.2006 }}</ref> It is the only target of these toxins.<ref name=":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.<ref name="pmc4280834" /><ref name=":0">{{cite journal | vauthors = Jørgensen R, Merrill AR, Andersen GR | title = The life and death of translation elongation factor 2 | journal = Biochemical Society Transactions | volume = 34 | issue = Pt 1 | pages = 1–6 | date = February 2006 | pmid = 16246167 | doi = 10.1042/BST20060001 }}</ref>

Diphthamide is biosynthesized from histidine and [[S-Adenosyl methionine|''S''-adenosyl methionine]] (SAM).<ref name="pmc4280834" /> The side chain bound to [[imidazole]] group and all [[Methyl group|methyl groups]] come from SAM. The whole synthesis takes place in three steps:<ref name="pmc4280834" />

* 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).<ref name="pmc4280834" />

==Biological function==

Diphthamide ensures [[Translation (biology)|translation]] fidelity.<ref name=pmc4280834>{{cite journal | vauthors = Su X, Lin Z, Lin H | title = The biosynthesis and biological function of diphthamide | journal = Critical Reviews in Biochemistry and Molecular Biology | volume = 48 | issue = 6 | pages = 515–521 | date = 2013-11-01 | pmid = 23971743 | pmc = 4280834 | doi = 10.3109/10409238.2013.831023 }}</ref>

The presence or absence of diphthamide is known to affect [[NF-κB]] or death receptor pathways.<ref name=":1">{{cite journal | vauthors = 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 | display-authors = 6 | title = Loss of diphthamide pre-activates NF-κB and death receptor pathways and renders MCF7 cells hypersensitive to tumor necrosis factor | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 34 | pages = 10732–10737 | date = August 2015 | pmid = 26261303 | pmc = 4553792 | doi = 10.1073/pnas.1512863112 | doi-access = free | bibcode = 2015PNAS..11210732S }}</ref>

== References ==

{{Reflist}}

[[Category:Post-translational modification]]

[[Category:Zwitterions]]