Structure and reactivity in the non-mevalonate pathway of isoprenoid biosynthesis.

Abstract

The function, structure and mechanism of two Escherichia coli enzymes involved in the non-mevalonate route of isoprenoid biosynthesis, 2C-methyl-D-erythritol 4-phosphate cytidylyltransferase and 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase, are reviewed. Comparisons of each with enzymes from microbial pathogens highlight important conservation of sequence suggestive of similarities in secondary structure, subunit folds, quaternary structure and active sites. Since both enzymes are validated drug targets, the models provide templates for structure-based design of anti-microbial agents targeting a number of serious human diseases.