YBR246W is required for the third step of diphthamide biosynthesis

J Am Chem Soc. 2012 Jan 18;134(2):773-6. doi: 10.1021/ja208870a. Epub 2011 Dec 21.

Abstract

Diphthamide, the target of diphtheria toxin, is a post-translationally modified histidine residue that is found in archaeal and eukaryotic translation elongation factor 2. The biosynthesis and function of this modification has attracted the interest of many biochemists for decades. The biosynthesis has been known to proceed in three steps. Proteins required for the first and second steps have been identified, but the protein(s) required for the last step have remained elusive. Here we demonstrate that the YBR246W gene in yeast is required for the last step of diphthamide biosynthesis, as the deletion of YBR246W leads to the accumulation of diphthine, which is the enzymatic product of the second step of the biosynthesis. This discovery will provide important information leading to the complete elucidation of the full biosynthesis pathway of diphthamide.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Gene Deletion
  • Gene Expression Regulation, Fungal / physiology*
  • Histidine / analogs & derivatives*
  • Histidine / biosynthesis
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*

Substances

  • RRT2 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Vesicular Transport Proteins
  • Histidine
  • diphthamide
  • diphthine