Aquaporins from pathogenic protozoan parasites: structure, function and potential for chemotherapy.
Infectious diseases, caused by protozoa, such as malaria, sleeping sickness, Chagas' disease or leishmaniasis, are a global threat. The increase in the number of affected individuals and the rapid spread of drug-resistant strains call for specific novel strategies to combat human pathogenic parasites. In the search for novel drug targets, transport proteins for nutrients and metabolites of the parasite-host interface are getting into focus. The present review summarizes and discusses the currently available results on protozoan aquaporins. Various genes coding for aquaporin water and solute channels have been identified in the protozoan genomes and they are probable elements of the parasite's cell membrane. Phylogenetic analysis reveals that individual aquaporin genes are of bacterial or plant origin. So far, six protozoan aquaporins have been cloned and functionally characterized. Typically, these are bifunctional channels and pass water at intermediate to high rates as well as uncharged solutes. In the present review, amino acid compositions of the individual pore entries are compared and permeability properties are attributed to specific protein features. Furthermore, possible physiological roles in osmotic protection and metabolism are discussed. Finally, the potential of protozoan aquaporins for use as a target or entry pathway for chemotherapeutic compounds is reviewed.
Beitz
Eric
E
Department of Pharmaceutical Chemistry, University of Tübingen, Morgenstelle 8, D-72076 Tübingen, Germany. eric.beitz@uni.tuebingen.de
D000595:Amino Acid Sequence; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology; D020346:Aquaporins / Q000502:physiology*; D018360:Crystallography, X-Ray; D056890:Eukaryota / Q000378:metabolism*; D005990:Glycerol / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009995:Osmosis; D010539:Permeability; D010802:Phylogeny; D010961:Plasmodium / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014345:Trypanosoma / Q000378:metabolism; D014867:Water / Q000737:chemistry / Q000378:metabolism
D000981:Antiprotozoal Agents; D020346:Aquaporins; D014867:Water; D005990:Glycerol