The Scripps Research Institute (TSRI) scientists through a high-resolution structure showed 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 but nobody knew exactly how.
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 synthesise 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," researcher Paul Schimmel said in a statement.
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.
The study was published in the journal Nature.