1-Deoxy-D-xylulose 5-phosphate synthase catalyzes a novel random sequential mechanism

Leighanne A. Brammer, Jessica M. Smith, Herschel Wades, Caren Freel Meyers

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Emerging resistance of human pathogens to anti-infective agents make it necessary to develop new agents to treat infection. The methylerythritol phosphate pathway has been identified as an anti-infective target, as this essential isoprenoid biosynthetic pathway is widespread in human pathogens but absent in humans. The first enzyme of the pathway, 1-deoxy-D-xylulose 5-phosphate (DXP) synthase, catalyzes the formation of DXP via condensation of D-glyceraldehyde 3-phosphate (D-GAP) and pyruvate in a thiamine diphosphate-dependent manner. Structural analysis has revealed a unique domain arrangement suggesting opportunities for the selective targeting of DXP synthase; however, reports on the kinetic mechanism are conflicting. Here, we present the results of tryptophan fluorescence binding and kinetic analyses of DXP synthase and propose a new model for substrate binding and mechanism. Our results are consistent with a random sequential kinetic mechanism, which is unprecedented in this enzyme class.

Original languageEnglish (US)
Pages (from-to)36522-36531
Number of pages10
JournalJournal of Biological Chemistry
Issue number42
StatePublished - Oct 21 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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