Transformation of a wobble 2-thiouridine to 2-selenouridine via S-geranyl-2-thiouridine as a possible cellular pathway

Bioorg Chem. 2014 Oct:56:49-53. doi: 10.1016/j.bioorg.2014.05.012. Epub 2014 Jun 6.

Abstract

The newly discovered S-geranylated 2-thiouridines (geS2U) (Dumelin et al., 2012) and 2-selenouridines (Se2U) were recently shown to be synthesized by a single enzyme (selenouridine synthase, SelU) through two distinct pathways using the same 2-thiouridine substrate (S2U); however, no clear catalytic mechanism was proposed. We suggest that S-geranyl-2-thiouridine is an intermediate of the SelU-catalyzed conversion of S2U to Se2U. The successful chemical transformation of S2U→geS2U→Se2U is demonstrated here as an initial approximation of the intracellular pathway. The structure of Se2U was confirmed by spectroscopic methods, which included, for the first time, (77)Se NMR data (δ 354ppm).

Keywords: 2-Selenouridine; 2-Thiouridine; 77Se NMR; S-alkylation; S-geranyl-2-thiouridine; SelU; Selenium chemical shift; Selenouridine synthase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biosynthetic Pathways
  • Cells / enzymology
  • Cells / metabolism*
  • Molecular Structure
  • Organoselenium Compounds / chemical synthesis*
  • Organoselenium Compounds / chemistry
  • Organoselenium Compounds / metabolism*
  • Terpenes / chemistry*
  • Terpenes / metabolism*
  • Thiouridine / analogs & derivatives*
  • Thiouridine / chemistry
  • Thiouridine / metabolism
  • Uridine / analogs & derivatives*
  • Uridine / chemical synthesis
  • Uridine / chemistry
  • Uridine / metabolism

Substances

  • 2-selenouridine
  • 2-thiouridine
  • Organoselenium Compounds
  • Terpenes
  • Thiouridine
  • Uridine