The bifunctional methylerythritol 4-phosphate cytidylyltransferase methylerythritol 2,4-cyclodiphosphate synthase (IspDF) is unusual in that it catalyzes nonconsecutive reactions in the 1-deoxy-d-xylulose 5-phosphate (DOXP) pathway of isoprenoid precursor biosynthesis. The crystal structure of IspDF from the bacterial pathogenCampylobacter jejunireveals an elongated hexamer withD3symmetry compatible with the dimeric 2C-methyl-d-erythritol-4-phosphate cytidylyltransferase and trimeric 2C-methyl-d-erythritol-2,4-cyclodiphosphate synthase monofunctional enzymes. Complex formation of IspDF with 4-diphosphocytidyl-2C-methyl-d-erythritol kinase (IspE), the intervening enzyme activity in the pathway, has been observed in solution for the enzymes fromC. jejuniandAgrobacterium tumefaciens. The monofunctional enzymes (2C-methyl-d-erythritol-4-phosphate cytidylyltransferase, IspE, and 2C-methyl-d-erythritol-2,4-cyclodiphosphate synthase) involved in the DOXP biosynthetic pathway ofEscherichia colialso show physical associations. We propose that complex formation of the three enzymes at the core of the DOXP pathway can produce an assembly localizing 18 catalytic centers for the early stages of isoprenoid biosynthesis.
Crystal structure of Escherichia coli PurE, an unusual mutase in the purine biosynthetic pathway