DXS as a target for structure-based drug design

Abstract

In this review, we analyze the enzyme DXS, the first and rate-limiting protein in the methylerythritol 4-phosphate pathway. This pathway was discovered in 1996 and is one of two known metabolic pathways for the biosynthesis of the universal building blocks for isoprenoids. It promises to offer new targets for the development of anti-infectives against the human pathogens, malaria or tuberculosis. We mapped the sequence conservation of 1-deoxy-xylulose-5-phosphate synthase on the protein structure and analyzed it in comparison with previously identified druggable pockets. We provide a recent overview of known inhibitors of the enzyme. Taken together, this sets the stage for future structure-based drug design.

Keywords: DXS; anti-infectives; antibiotics; malaria; methylerythritol phosphate pathway; protein crystallography; structure-based drug design; tuberculosis.