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.

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.

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