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Mechanism and inhibition of 1-deoxy-D-xylulose-5-phosphate reductoisomerase.

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.

journal_name

Bioorg Chem

journal_title

Bioorganic chemistry

authors

Murkin AS,Manning KA,Kholodar SA

doi

10.1016/j.bioorg.2014.06.001

subject

Has Abstract

pub_date

2014-12-01 00:00:00

pages

171-185

eissn

0045-2068

issn

1090-2120

pii

S0045-2068(14)00046-7

journal_volume

57

pub_type

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