ETH scientists uncover structure of synthase

Research Lead

The atomic structure of mammalian fatty acid synthase, a promising target for the development of anti-cancer and anti-obesity drugs and the treatment of metabolic disorders, has been determined by researchers at ETH Zürich.

With support from the National Centre of Excellence in Research (NCCR) in Structural Biology at the Swiss National Science Foundation, the researchers elucidated the structure using data collected at the Swiss Light Source (SLS) of the Paul Scherrer Institute (PSI) in Switzerland.

The results reveal the details of all catalytic active sites responsible for iterative fatty acid synthesis and show how the flexibility of this large multi-enzyme is used for transferring substrates from one enzymatic active site to the next.

In addition to the fundamental scientific interest in the function of this multi-enzyme, mammalian fatty acid synthase is also considered a promising drug target. Although most fat accumulated in animals and humans is delivered to cells by ingestion and not by de novo synthesis, compounds that inhibit the function of the mammalian fatty acid synthase induce weight reduction in animals, and thus show potential for the treatment of obesity and related diseases, such as Type II diabetes and cardiovascular disease. Furthermore, due to the increased requirement for fatty acid synthesis in cancer cells, inhibitors of this enzyme have anti-tumor activity, making fatty acid synthase an attractive drug target for anti-cancer therapy.