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Biological Chemistry

New Target For Malaria Drugs

Revelation of the essential role of a common enzyme in controlling disease transmission could lead to new medications

by Stu Borman
January 6, 2014 | APPEARED IN VOLUME 92, ISSUE 1

Scientists have discovered that an enzyme common to many life-forms could serve as a new biomolecular target for treating malaria. Novel treatments for the disease—which kills more than 1 million people globally each year—are urgently needed because some Plasmodium parasites that cause malaria have developed resistance to existing drugs. Edward W. Tate of Imperial College London and coworkers used chemical labeling techniques to track how the enzyme N-myristoyltransferase (NMT) adds the fatty acid myristate to a cell membrane protein in the major human malaria parasite P. falciparum, controlling production of a membrane complex essential for mosquito-to-human malaria transmission and long-term infection (Nat. Chem. 2013, DOI: 10.1038/nchem.1830). NMT is present in all eukaryotes, but the study for the first time demonstrates its essential role in this parasite and identifies compounds that potently block its activity. The researchers found that administering NMT inhibitors to malaria-infected mice prevented the animals from developing malaria symptoms and extended their life spans. NMT has many critical substrate proteins, Tate says, “and blocking it may provide a way to prevent long-term disease and transmission, in addition to treating acute malaria.” Tate and his colleagues are working to improve the potency of the inhibitors and believe an optimized version could be ready for clinical trials within four years.

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