Figure 1 - full size

 

Figure 1.
Fig. 1. a, methylerythritol phosphate and mevalonate pathway of isoprenoid biosynthesis. IPP ( 4) and DMAPP (5) are either synthesized from acetyl-CoA (7) via mevalonate (6) or from 1-deoxy-D-xylulose 5-phosphate (1) via 2-C-methyl-D-erythritol 4-phosphate (2) and (E)-1-hydroxy-2-methyl-but-2-enyl 4-diphosphate (3). b, stereochemical course of the reaction performed by IspC. 1-deoxy-D-xylulose 5-phosphate (1) is converted into 2-C-methyl-D-erythritol 4-phosphate (4) via the aldose intermediate 2-C-methyl-D-erythrose 4-phosphate (8) that is reduced by NADPH after isomerization. Route A for a fomidomycin-like binding of the intermediate 8 leads to the incorrect stereochemistry, whereas route B results in the correct stereochemistry. The migrating group (C-4) and the hydride from NADPH attack on opposite sites of C-2 and C-3, respectively. The asterisk indicates the hydride transferred from NADPH. c, chemical structures of the IspC inhibitors fosmidomycin (9) and FR-900098 (10).

The above figure is reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 18401-18407) copyright 2003.