Description
Plasmodium vivax remains a major cause of malaria worldwide and poses unique challenges for disease control due to its ability to form dormant liver-stage parasites (hypnozoites) that can reactivate months after initial infection. This capacity for relapse contributes significantly to the persistence and transmission of vivax malaria. As Plasmodium parasites depend heavily on pyrimidine nucleotide biosynthesis for growth and replication, enzymes within this pathway represent attractive targets for antimalarial drug development. Orotate phosphoribosyltransferase (OPRT) catalyzes the conversion of orotate and phosphoribosyl pyrophosphate (PRPP) to orotidine-5′-monophosphate (OMP), a key step in pyrimidine biosynthesis. In this study, we focus on the structural and functional characterization of the P. vivax OPRT (PvOPRT), which appears to exhibit atypical sequence and structural features compared with canonical OPRT enzymes. Bioinformatic analyses and structural modeling suggest the presence of unique insertions and loop regions that may influence substrate binding and catalytic activity. These differences may distinguish PvOPRT from the human enzyme and provide opportunities for selective inhibition. Ongoing work aims to experimentally characterize PvOPRT through biochemical and biophysical approaches to define its catalytic properties and structural organization. Understanding these unique features may support the development of targeted inhibitors against pyrimidine biosynthesis in P. vivax and contribute to new therapeutic strategies for vivax malaria.