Abstract
Isopentenyl pyrophosphate (IPP) and its isomer dimethylallyl pyrophosphate (DMAPP) are the common precursors for the synthesis of all isoprenoids. While IPP and DMAPP are produced by the mevalonate pathway in archaea, fungi, and animals, they are synthesized by a mevalonate-independent pathway in most bacteria, algae, and plant plastids. DXS (1-deoxy-d-xylulose 5-phosphate synthase) catalyzes the first and the rate-limiting step of the mevalonate-independent pathway and is an attractive target for the development of novel antibiotics, antimalarials, and herbicides. Crystal structures of DXS from E. coli and D. radiodurans, in complex with the coenzyme thiamine pyrophosphate (TPP), show that the enzyme contains three domains (I, II, and III), which share homology to the equivalent domains in transketolase and the E1 subunit of pyruvate dehydrogenase. However, DXS has a novel arrangement of these domains in the monomer and the dimer as compared to the other enzymes. The active site of DXS is located at the interface of domains I and II in the same monomer. The coenzyme TPP is mostly buried in the complex, but the C2 atom of its thiazolium ring is exposed to a solvent-accessible tunnel that is likely the substrate-binding site.
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Xiang, S., Usunow, G., Lange, G., Busch, M., Tong, L. (2012). 1-Deoxy-d-Xylulose 5-Phosphate Synthase (DXS), a Crucial Enzyme for Isoprenoids Biosynthesis. In: Bach, T., Rohmer, M. (eds) Isoprenoid Synthesis in Plants and Microorganisms. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4063-5_2
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