Functional characterization of Plasmodium vivax cationic amino acid transporter 1 (PvCAT1)

초록

Plasmodium vivax is the most widely distributed human malaria parasite. Blocking amino acid uptake has been suggested as a novel mode of action. Therefore, the purpose of this study is functional characterization of a cationic amino acid, arginine transporter (PvCAT1), of Plasmodium vivax.From the NCBI protein database, the amino acid transporter ApiAT8 (protein No. VUZ93331) was selected. The PvCAT1 cDNA consists of 1716 base pairs, encoding a 571-amino acid residue protein having 12 putative transmembrane-spanning domains. When expressed in?Xenopus?oocytes, radiolabeled arginine uptake observed in a time-dependent manner, based on both expression time and incubation time, and was sodium-independent. PvCAT1 showed no exchange mode in efflux experiments. Non-linear regression analysis revealed a Km value of 17.5 mM and a Vmax value of 25 pmol/oocyte/hr. Inhibition experiments showed a strong inhibitory effect by arginine and lysine. These findings provide insights into the properties of arginine uptake via PvCAT1 and support approaches to vivax malaria drug development strategy targeting the PvCAT1 to starve the parasite.