Mechanism and Inhibition of 1-deoxy-D-xylulose-5-phosphate Reductoisomerase

Andrew S Murkin, Kathryn A Manning, Svetlana A Kholodar

Bioorg Chem. 2014 Dec;57:171-185.

PMID: 24998420

Abstract:

The non-mevalonate or 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway is responsible for generating isoprenoid precursors in plants, protozoa, and bacteria. Because this pathway is absent in humans, its enzymes represent potential targets for the development of herbicides and antibiotics. 1-Deoxy-d-xylulose (DXP) reductoisomerase (DXR) is a particularly attractive target that catalyzes the pathway's first committed step: the sequential isomerization and NADPH-dependent reduction of DXP to MEP. This article provides a comprehensive review of the mechanistic and structural investigations on DXR, including its discovery and validation as a drug target, elucidation of its chemical and kinetic mechanisms, characterization of inhibition by the natural antibiotic fosmidomycin, and identification of structural features that provide the molecular basis for inhibition of and catalysis.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP60299436	1-Deoxy-D-xylulose		60299-43-6	Price