Document Type
Article
Publication Date
4-2016
Keywords
1-Deoxy-d-xylulose-5-phosphate synthase, Methylerythritol phosphate pathway, Isoprenoids, Malaria, Plasmodium vivax, Plasmodium, falciparum
Digital Object Identifier (DOI)
https://doi.org/10.1016/j.pep.2015.12.003
Abstract
We have successfully truncated and recombinantly-expressed 1-deoxy-D-xylulose-5-phosphate synthase (DXS) from both Plasmodium vivax and Plasmodium falciparum. We elucidated the order of substrate binding for both of these ThDP-dependent enzymes using steady-state kinetic analyses, dead-end inhibition, and intrinsic tryptophan fluorescence titrations. Both enzymes adhere to a random sequential mechanism with respect to binding of both substrates: pyruvate and D-glyceraldehyde-3-phosphate. These findings are in contrast to other ThDP-dependent enzymes, which exhibit classical ordered and/or ping-pong kinetic mechanisms. A better understanding of the kinetic mechanism for these two Plasmodial enzymes could aid in the development of novel DXS-specific inhibitors that might prove useful in treatment of malaria.
Rights Information
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Protein Expression and Purification, v. 120, p. 16-27
This article is the post-print author version. Under a Creative Common license.
Scholar Commons Citation
Battistini, Matthew R.; Shoji, Christopher; Handa, Sumit; Breydo, Leonid; and Merkler, David J., "Mechanistic Binding Insights for 1-deoxy-D-Xylulose-5-PhosphateSynthase, the Enzyme Catalyzing the First Reaction of Isoprenoid Biosynthesis in the Malaria-causing Protists, Plasmodium falciparum and Plasmodium vivax" (2016). Chemistry Faculty Publications. 27.
https://digitalcommons.usf.edu/chm_facpub/27
