1-Deoxy-D-xylulose 5-phosphate Synthase Catalyzes a Novel Random Sequential Mechanism

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2011 Sep 1

PMID 21878632

Citations 43

Authors

Leighanne A Brammer

Jessica M Smith

Herschel Wade

Caren Freel Meyers

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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