Isoprenoids (or terpenoids) are a large and structurally diverse class of biomolecules that are essential for the survival of all forms of life. Despite the vast differences in their final structures and functions, the early steps of isoprenoid biosynthesis in all organisms follow one
of only two known biosynthetic pathways: the mevalonate pathway or the methyl erythritol phosphate (MEP) pathway. Interestingly, while humans utilize the mevalonate pathway, many human pathogens rely exclusively on the MEP pathway for the biosynthesis of their isoprenoid compounds. This has
led to a number of mechanistic studies of the MEP-specific pathway enzymes, with the ultimate goal of developing small molecule inhibitors as potential drugs. In addition to their therapeutic value, many of the MEP pathway enzymes also catalyze unusual chemical transformations that are not
well understood. In this review, we will highlight the recent work by us and others towards the elucidation of the catalytic mechanisms of several key enzymes involved in the early stages of isoprenoid biosynthesis. These include 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) and 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate
reductase (IspH) of the MEP pathway, and the type II isopentenyl diphosphate:dimethylallyl diphosphate isomerase (IDI-2) from Staphylococcus aureus. The functions of these enzymes are validated or identified as potential drug targets.
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Document Type: Research Article
Publication date: June 1, 2009
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International Journal for Chemistry and Official Membership Journal of the Swiss Chemical Society (SCS) and its Divisions
CHIMIA, a scientific journal for chemistry in the broadest sense, is published 10 times a year and covers the interests of a wide and diverse readership. Contributions from all fields of chemistry and related areas are considered for publication in the form of Review Articles and Notes. A characteristic feature of CHIMIA are the thematic issues, each devoted to an area of great current significance.
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