Bisubstrate Analog Inhibitors of DXP Synthase Show Species Specificity.

ABSTRACT: 1-Deoxy-d-xylulose 5-phosphate synthase (DXPS) is a unique thiamin diphosphate (ThDP)-dependent enzyme that catalyzes the formation of DXP, a branchpoint metabolite required for the biosynthesis of vitamins and isoprenoids in bacterial pathogens. DXPS has relaxed substrate specificity and utilizes a gated mechanism, equipping DXPS to sense and respond to diverse substrates. We speculate that pathogens utilize this distinct gated mechanism in different ways to support metabolic adaptation during infection. DXPS is susceptible to time-dependent inhibition by bisubstrate analogs. We suggest that potential differences in the ligand-gated mechanism that may accompany alternative activities of DXPS homologues may enable the development of species-specific bisubstrate analog inhibitors. Here, we

SUBMITTER: Henriquez S 

PROVIDER: S-EPMC11806520 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature