Mammalian fatty acid synthase is one of the most complex molecular synthetic machines in human cells. It is also a promising target for the development of anti-cancer and anti-obesity drugs and the treatment of metabolic disorders. Now researchers at ETH Zurich have determined the atomic structure of a mammalian fatty acid synthase. Their results have just been published in Science magazine.
Synthesis of fatty acids is a central cellular process that has been studied for many decades. Fatty acids are used in the cell as energy storage compounds, messenger molecules and building blocks for the cellular envelope. Until now, individual steps of this process have been investigated using isolated bacterial enzymes. However, in higher organisms except plants fatty acid synthesis is catalyzed by large multifunctional proteins where many individual enzymes are brought together to form a "molecular assembly line".
The atomic structure is the result of many years of research
As described in this week's issue of "Science" magazine, researchers at ETH Zurich, supported by the National Centre of Excellence in Research (NCCR) in Structural Biology at the Swiss National Science Foundation, determined the high-resolution structure of a mammalian fatty acid synthase using data collected at the Swiss Light Source (SLS) of the Paul Scherrer Institute (PSI) in Switzerland. These results crown the efforts begun in 2001 to determine the detailed structures of fatty acid synthases in higher organisms by a relatively small group of scientists at ETH Zurich. The group, consisting of Timm Maier, Marc Leibundgut and Simon Jenni in the laboratory of Prof. Nenad Ban, published their first papers describing architectures of fungal and mammalian fatty acid synthases two years ago. That was followed last year by two papers on the atomic structures of fungal fatty acid synthases and the mechanism of substrate shuttling and delivery in these multi-enz
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ETH Zurich/Swiss Federal Institute of Technology