Structures of two archaeal diphthine synthases: Insights into the post-translational modification of elongation factor 2

Seiichiro Kishishita, Katsumi Shimizu, Kazutaka Murayama, Takaho Terada, Mikako Shirouzu, Shigeyuki Yokoyama, Naoki Kunishima

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

The target of diphtheria toxin is the diphthamide residue in translation elongation factor 2 (EF-2), which is generated by a three-step post-translational modification of a specific histidine residue in the EF-2 precursor. In the second modification step, an S-adenosylmethionine-dependent methyltransferase, diphthine synthase (DS), catalyzes the trimethylation of the EF-2 precursor. The homodimeric crystal structures of the archaeal diphthine synthases from Pyrococcus horikoshii OT3 and Aeropyrum pernix K1 have been determined. These structures share essentially the same overall fold as the cobalt-precorrin-4 methyltransferase CbiF, confirming that DS belongs to the dimeric class III family of methyltransferases. In the P. horikoshii DS dimer, only one of the two active sites binds the reaction product S-adenosyl-l- homocysteine (AdoHcy), while the other active site contains no ligand. This asymmetric AdoHcy binding may be a consequence of intra-domain and inter-domain movements upon binding of AdoHcy at one of the two sites. These movements disrupt the twofold dimeric symmetry of the DS dimer and probably cause lower AdoHcy affinity at the other binding site.

Original languageEnglish
Pages (from-to)397-406
Number of pages10
JournalActa Crystallographica Section D: Biological Crystallography
Volume64
Issue number4
DOIs
Publication statusPublished - 2008 Mar 19
Externally publishedYes

Keywords

  • Diphthamide
  • Diphtheria toxin
  • EF-2
  • Methyltransferases

ASJC Scopus subject areas

  • Structural Biology

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