Dr. Meshnick and co-workers have identified one of the artemisinin target proteins as a Translationally Controlled Tumor Protein (TCTP) homolog. This Plasmodium falciparum TCTP has been cloned and sequenced, and purified recombinant TCTP has been obtained. Antibody to recombinant TCTP immunoprecipitates (3H) dihydroartemisinin-TCTP complex from drug-treated parasites.
Aim 1 is to further characterize the P. falciparum TCTP, building on recent observations that it binds with artemisinin, heme, and calcium. Accordingly they will attempt to determine the subcellular localization of TCTP, and determine the affinity of TCTP for calcium and other ligands. They will attempt to identify where artemisinin forms its covalent bonds in TCTP and determine how artemisinin affects TCTP function. Studies involving comparisons with the human TCTP and with genetically engineered mutant reconbinant TCTPs are also planned.
| Bhisutthibhan, J; Meshnick, S R (2001) Immunoprecipitation of [(3)H]dihydroartemisinin translationally controlled tumor protein (TCTP) adducts from Plasmodium falciparum-infected erythrocytes by using anti-TCTP antibodies. Antimicrob Agents Chemother 45:2397-9 |
