Final Report Summary - MalariaPorin (Validation of the Plasmodium aquaglyceroporin as a drug target)
By analysing genome data from Plasmodium falciparum the coordinator of MalariaPorin has identified a single water/glycerol channel, PfAQP, which is the only member of the aquaporin family encoded in the Plasmodium falciparum genome. Immunolabeling showed its presence at the parasite/host interface. The PfAQP protein belongs to the major facilitator super family for nutrients and metabolites and is a bi-functional pore with high permeability for water and glycerol. The fact that the aquaglyceroporin is a component of the reduced interface strongly suggests basic functions in the parasite biochemistry.
The channel may play important roles in three essential cellular processes:
- protection against osmotic stress
- access to the serum glycerol pool as a precursor for lipid synthesis and
- glycerol uptake and oxidation to cope with oxidative stress.
Major achievements can be summarised in that the project, enhanced knowledge about the physiological role of aquaglyceroporins in plasmodia, identified aquaporin protein structures that are involved in inhibitor binding, optimised the throughput of assay systems for testing potential aquaporin blockers and, created novel lead compounds for antimalarial chemotherapy.