Singapore: The mysterious inner workings of Chang Shan, a Chinese herbal medicine used to treat fevers associated with malaria, have been uncovered thanks to a high-resolution structure solved at The Scripps Research Institute. The institute is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences.

Described in the journal Nature, the structure shows in atomic detail how a two-headed compound derived from the active ingredient in Chang Shan works. Scientists have known that this compound, called halofuginone (a derivative of the febrifugine), can suppress parts of the immune system.

The new structure shows that, like a wrench in the works, halofuginone jams the gears of a molecular machine that carries out aminoacylation, a crucial biological process that allows organisms to synthesize the proteins they need to live. Chang Shan, also known as Dichroa febrifuga Lour, probably helps with malarial fevers because traces of a halofuginone-like chemical in the herb interfere with this same process in malaria parasites, killing them in an infected person's bloodstream.

"Our new results solved a mystery that has puzzled people about the mechanism of action of a medicine that has been used to treat fever from a malaria infection going back probably 2,000 years or more," said Dr Paul Schimmel, the Ernest and Jean Hahn Professor and Chair of Molecular Biology and Chemistry and member of The Skaggs Institute for Chemical Biology at the Scripps institute. Dr Schimmel led the research with the institute's postdoctoral fellow Dr Huihao Zhou.

Halofuginone has been in clinical trials for cancer, but the high-resolution picture of the molecule suggests it has a modularity that would make it useful as a template to create new drugs for numerous other diseases.