Evidence that oxidative dephosphorylation by the nonheme Fe(II), α-ketoglutarate:UMP oxygenase occurs by stereospecific hydroxylation

Anwesha Goswami, Xiaodong Liu, Wenlong Cai, Thomas P. Wyche, Tim S. Bugni, Maïa Meurillon, Suzanne Peyrottes, Christian Perigaud, Koichi Nonaka, Jürgen Rohr, Steven G. Van Lanen

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

LipL and Cpr19 are nonheme, mononuclear Fe(II)-dependent, α-ketoglutarate (αKG):UMP oxygenases that catalyze the formation of CO2, succinate, phosphate, and uridine-5′-aldehyde, the last of which is a biosynthetic precursor for several nucleoside antibiotics that inhibit bacterial translocase I (MraY). To better understand the chemistry underlying this unusual oxidative dephosphorylation and establish a mechanistic framework for LipL and Cpr19, we report herein the synthesis of two biochemical probes—[1′,3′,4′,5′,5′-2H]UMP and the phosphonate derivative of UMP—and their activity with both enzymes. The results are consistent with a reaction coordinate that proceeds through the loss of one 2H atom of [1′,3′,4′,5′,5′-2H]UMP and stereospecific hydroxylation geminal to the phosphoester to form a cryptic intermediate, (5′R)-5′-hydroxy-UMP. Thus, these enzyme catalysts can additionally be assigned as UMP hydroxylase-phospholyases.

Original languageEnglish
Pages (from-to)468-478
Number of pages11
JournalFEBS Letters
Volume591
Issue number3
DOIs
StatePublished - Feb 1 2017

Bibliographical note

Publisher Copyright:
© 2017 Federation of European Biochemical Societies

Keywords

  • antibiotic
  • biosynthesis
  • nonheme iron
  • nucleoside
  • oxygenase
  • translocase I

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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