The isoprenoid biosynthetic pathway yields diverse natural products essential to all living organisms. Isopentenyl pyrophosphate (IPP) is a precursor that is generated from the melavonate pathway; however, an alternate melavonate-independent pathway was recently discovered in most bacteria, algae, and plant chloroplasts. The first commited precursor is 2-C-methyl-D-erythritol 4-phosphate (MEP). The MEP pathway is absent in animals, so it provides a lucrative drug target for the development of antibiotics, antimalarials, and herbicides. 1-Deoxy-D-xylulose 5-phosphate synthase (DXS) catalyzes the rate-limiting step in the MEP pathway.
X-ray crystallographic structure of DXS dimer from PDB 201S (E. coli): each monomer being a gold and green color; the gold monomer has a surface rendition. Potassium is represented with a purple sphere while Magnesium is represented with a light green sphere. Ligands can be observed near the Magnesium ions.
Green monomer only from above with bound thymidine diphosphate (with cyan carbon molecules).
Close-up view of thymidine diphosphate in the DXS active site. The active site is represented with a mesh rendition of nearby interacting residues.
Close-up view of thymidine diphosphate in the DXS active site. The active site is represented with a stick rendition of nearby interacting residues. Per PDBsum, residues with stronger residues are colored with the darker green. Note the coordination of the pyrophosphate with the Magnesium ion and the pi stacking of thymidine with the nearby phenylalanine residue.
Close-up view of thymidine diphosphate in the DXS active site combining both mesh and stick representations from above.