Cloning, expression, and characterization of a polyprenyl diphosphate synthase from Toxoplasma gondii
Behera, Ranjan Kumar
MetadataShow full item record
Toxoplasma gondii is an opportunistic protozoan parasite of fetuses from infected mothers and of immuno-compromised patients. Limitations of current treatments and unavailability of a suitable vaccine necessitate discovery of novel targets and development of new drugs. The isoprenoid pathway of T. gondii, being unique and essential, could be exploited for therapeutic intervention. Recently, we have characterized a polyprenyl diphosphate synthase from T. gondii (TgPPS), as a target of bisphosphonates. We cloned the TgPPS gene homologous to polyprenyl synthases from other organisms, expressed it in Escherichia coli, and characterized the recombinant-TgPPS. Our results show that TgPPS is a soluble protein and localizes to the cytoplasm of the parasite. We propose that TgPPS is a heptaprenyl diphosphate synthase, and may synthesize the isoprenoid side chain of ubiquinone. Our in vitro enzyme inhibition study demonstrates that TgPPS is inhibited by many bisphosphonates, which justifies the potential of TgPPS as a putative drug target.