The biosynthesis and biological function of diphthamide

Xiaoyang Su, Zhewang Lin, Hening Lin

Research output: Contribution to journalReview articlepeer-review

44 Scopus citations


Eukaryotic and archaeal elongation factor 2 contains a unique post-translationally modified histidine residue, named diphthamide. Genetic and biochemical studies have revealed that diphthamide biosynthesis involves a multi-step pathway that is evolutionally conserved among lower and higher eukaryotes. During certain bacterial infections, diphthamide is specifically recognized by bacterial toxins, including diphtheria toxin, Pseudomonas exotoxin A and cholix toxin. Although the pathological relevance is well studied, the physiological function of diphthamide is still poorly understood. Recently, many new interesting developments in understanding the biosynthesis have been reported. Here, we review the current understanding of the biosynthesis and biological function of diphthamide.

Original languageEnglish (US)
Pages (from-to)515-521
Number of pages7
JournalCritical Reviews in Biochemistry and Molecular Biology
Issue number6
StatePublished - Nov 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology


  • Diphthamide
  • Diphtheria toxin
  • Diphthine
  • Post-translational modifications
  • Radical SAM enzyme


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