Disease relevance of PF11_0338

• A single, bi-functional aquaglyceroporin in blood-stage Plasmodium falciparum malaria parasites [1].
• We identified a single aquaglyceroporin (PfAQP) in the nearly finished genome of P. falciparum with highest similarity to the Escherichia coli glycerol facilitator (50.4%), but both canonical Asn-Pro-Ala (NPA) motifs in the pore region are changed to Asn-Leu-Ala (NLA) and Asn-Pro-Ser (NPS), respectively [1].

High impact information on PF11_0338

• Molecular dissection of water and glycerol permeability of the aquaglyceroporin from Plasmodium falciparum by mutational analysis [2].
• Within a conserved WET triad in the extracellular C-loop we identified a Plasmodium aquaglyceroporin-specific glutamate (E125) located in proximity to a conserved arginine (R196) at the pore mouth [2].
• We use point mutations to demonstrate that amino acids directly lining the pore are not responsible for the excellent water permeability of the Plasmodium aquaglyceroporin but affect permeability of pentitols [2].
• Further, a yeast strain lacking the endogenous aquaglyceroporin (Fps1) is rescued by expression of PfAQP which provides for the efflux of toxic methylamine [3].
• Mechanisms responsible for transport of substrates into intraerythrocytic parasites have also been clarified by studies of three substrate-specific (hexose, nucleoside and aquaglyceroporin) parasite plasma membrane transporters [4].

Associations of PF11_0338 with chemical compounds

• Dihydroxyacetone and methylglyoxal as permeants of the Plasmodium aquaglyceroporin inhibit parasite proliferation [5].
• Earlier we characterized an aquaglyceroporin from Plasmodium falciparum with high permeability for both glycerol and water [2].

References