Human fatty acid unravelled, paving way to new drugsSeptember 6th, 2008 - 3:34 pm ICT by IANS
London, Sep 6 (IANS) Researchers have determined the atomic structure of mammalian fatty acid synthase or MFAS - a complex synthetic machine in human cells - paving the way for developing anti-cancer, anti-obesity drugs and the treatment of metabolic disorders. MFAS belongs to a large family of multi-enzymes, some of which are responsible for the synthesis of complex natural products with antibiotic, anti-cancer, anti-fungal and immunosuppressive properties that are of outstanding medical relevance.
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 catalysed by large multifunctional proteins where many individual enzymes are brought together to form a “molecular assembly line”.
ETH Zurich researchers, supported by 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 (MFAS), relying on 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 comprising Timm Maier, Marc Leibundgut and Simon Jenni in the laboratory of Nenad Ban published their first papers describing architectures of fungal and MFAS two years ago.
Besides, MFAS is also considered a promising drug target. Although most fat accumulated in animals and humans is delivered to cells by ingestion, compounds that inhibit MFAS function induce weight reduction in animals, showing potential in obesity and obesity-related diseases, such as diabetes and coronary disorders.
Their results have just been published in Science magazine.