Chloroquine, an antimalarial developed during the 1930s, was in many senses a 'wonder drug' - cheap, effective, and with minimal side effects. By the 1950s, however, malaria parasites emerged that were resistant to chloroquine. Since then chloroquine-resistant parasites have spread slowly but surely throughout endemic areas, and the drug is now virtually useless in the places where it is most-needed.

Chloroquine resistance arises as a result of mutations in a protein christened the 'chloroquine resistance transporter'. This protein sits in the membrane enclosing an internal compartment in the parasite, though what it is doing there, and how changes in this protein confer chloroquine resistance to the parasite is unclear. In this 'bioinformatic' study we have shown that the protein is actually a member of a large family of proteins which, in other organisms have the job of moving small molecules across membranes. Other members of the family have the same general shape and configuration as the chloroquine resistance transporter, and it is clear from studies on other family members that the changes that give rise to chloroquine resistance are in a part of the protein that determines the size, shape and electrical charge of the molecules that that protein can carry across the membrane. This has led to the hypothesis that mutations in the chloroquine resistance transporter change the protein in such a way as to allow it to carry chloroquine out of the compartment in which it exerts its antimalarial effect, thereby decreasing the effectiveness of the drug.

This paper has attracted a number of commentaries (Drug Discovery Today, 9, 814-5; Faculty of 1000).

Martin, R.E. and Kirk, K. (2004) The malaria parasite's chloroquine resistance transporter is a member of the drug/metabolite transporter superfamily. Molecular Biology and Evolution, 21: 1938-1949.