The Plasmodium falciparum translationally controlled tumor protein homolog and its reaction with the antimalarial drug artemisinin.

Article Details

Citation

Bhisutthibhan J, Pan XQ, Hossler PA, Walker DJ, Yowell CA, Carlton J, Dame JB, Meshnick SR

The Plasmodium falciparum translationally controlled tumor protein homolog and its reaction with the antimalarial drug artemisinin.

J Biol Chem. 1998 Jun 26;273(26):16192-8.

PubMed ID
9632675 [ View in PubMed
]
Abstract

Artemisinin and its derivatives are important new antimalarial drugs. When Plasmodium falciparum-infected erythrocytes are incubated with [10-3H]dihydroartemisinin, several malaria-specific proteins become labeled. One of these proteins is the P. falciparum translationally controlled tumor protein (TCTP) homolog. In vitro, dihydroartemisinin reacts covalently with recombinant TCTP in the presence of hemin. The association between drug and protein increases with increasing drug concentration, plateauing at approximately 1 drug/TCTP molecule. By Scatchard analysis, there appear to be 2 hemin binding sites on TCTP with dissociation constants of approximately 18 microM. When the single cysteine moiety is blocked by pretreatment with iodoacetamide, hemin binding is not affected, whereas drug binding is reduced by two-thirds. Thus, TCTP reacts with artemisinin in situ and in vitro in the presence of hemin and appears to bind to hemin. The function of the malarial TCTP and the role of this reaction in the mechanism of action of artemisinin await elucidation.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
ArtenimolTranslationally-controlled tumor protein homologProteinPlasmodium falciparum (isolate 3D7)
Unknown
Ligand
Details