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Biological Chemistry

Protein Complex Drives Malaria Detox

Malaria parasite converts hemoglobin to hemozoin with five-protein complex

by Celia Henry Arnaud
March 11, 2013 | A version of this story appeared in Volume 91, Issue 10

The malaria parasite gets amino acids by breaking down hemoglobin in its host’s red blood cells. The free heme released in the process is a toxin to the parasite, which detoxifies the heme by polymerizing it into a crystalline substance called hemozoin. A team of researchers led by Pawan Malhotra of the International Center for Genetic Engineering & Biotechnology in New Delhi proposes that a 200-kilodalton protein complex in the parasite’s food vacuole directs this detoxification (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.1218412110). By using coimmunoprecipitation and mass spectrometry, the team found that the complex contains four hemoglobin-degrading proteases associated with heme detoxification protein (HDP), which forms hemozoin from free heme. The researchers developed an in vitro assay for hemozoin formation by combining HDP with a recombinant version of falcipain 2, one of the proteases. They used the assay to assess the modes of action of two antimalarial drugs, chloroquine and artemisinin. The assay shows that chloroquine blocks hemoglobin degradation by inhibiting hemoglobin binding to falcipain 2 and by forming a complex with free heme, whereas artemisinin blocks heme polymerization by binding to free heme.

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