Structural and biochemical characterization of FK506 binding protein (FKBP) from plasmodium falciparum any) plasmodium vivax.

Abstract

Plasmodium falciparum and Plasmodium vivax are two major malaria causing species and develop resistance to currently available antimalarial drugs. This prompts a need to identify parasitic proteins that could serve as novel targets to design antimalarial drugs. Previous studies have demonstrated that FK506 and rapamycin exhibit antimalarial effects, suggesting the presence of FK506 binding protein (FKBP) homolog in the parasite. Recently FKBP protein with molecular weight of 35 kDa has been identified in P. falciparum (P/FKBP35) and its homolog in P. vivax was also identified by our group (PvFKBP35). FK506 binding protein (FKBP) family is one of the major families of immunophilins, which binds to the immunosuppressive drug FK506. FKBPs are largely distributed in different eukaryotes and perform important physiological functions. FKBPs show peptidylprolyl cis-trans isomerase (PPIase) and chaperonic activities. FKBPs also act as co-chaperones and interact with Hsp90, suggesting the role of FKBPs in protein folding and assembly of proteins. P/FKBP35 and PvFKBP35 consist of N-terminal FK506 binding domain (FKBD) followed by tetratricopeptide repeats (TPR) domain and calmodulin binding domain (CaM). Genome analysis of P. falciparum and P. vivax revealed the presence of only one FKBP protein in the parasites. P/FKBP35 and PvFKBP35 proteins could be important for physiological functions of the parasite. Currently, the role and function of the proteins in the parasites remain to be further explored.