title: YBR246W is required for the third step of diphthamide biosynthesis.
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.
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Su
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Wankyu
authors.initials: W
authors.lastname: Lee
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.forename: Hening
authors.initials: H
authors.lastname: Lin
mesh_terms: D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D006639:Histidine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C570231:RRT2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; D006639:Histidine; C027527:diphthamide; C027529:diphthine