�Mammalian fatso acid synthase is peerless of the most building 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 fat person 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 separated bacterial enzymes. However, in higher organisms except plants fatty acidic synthesis is catalyzed by large multifunctional proteins where many item-by-item enzymes ar brought in concert to configuration a "molecular assembly line".
The atomic body structure is the result of many days 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, dictated the high-resolution structure of a mammalian fatty acrid synthase exploitation data gathered at the Swiss Light Source (SLS) of the Paul Scherrer Institute (PSI) in Switzerland. These results crown the efforts begun in 2001 to find the detailed structures of fatty caustic synthases in higher organisms by a relatively small group of scientists at ETH Zurich. The mathematical group, consisting of Timm Maier, Marc Leibundgut and Simon Jenni in the research laboratory of Prof. Nenad Ban, published their first written document describing architectures of fungous and mammal fatty acid synthases two years ago. That was followed last year by two document on the atomic structures of fungous fatty virulent synthases and the mechanism of substratum shuttling and delivery in these multi-enzymes. Now this latest publication describes the atomic social structure of the mammalian fatso acid synthase. These results reveal the details of all catalytic active sites responsible for iterative fatso acid deduction and shew how the flexibility of this large multi-enzyme is used for transferring substrates from one and only enzymatic active site to the next. The structure can be considered a milestone for future inquiry in the field.
Fatty acid synthases as drug targets?
In addition to the cardinal scientific involvement in the function of this multi-enzyme that plays a central role in primary metabolism, mammalian fat person acid synthase is as well considered a promising dose 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 occasion of the mammalian roly-poly acid synthase induce weight reduction in animals, showing potential for the treatment of corpulency and obesity-related diseases, such as diabetes and coronary thrombosis disorders. Furthermore, due to the increased requirement for fatty sulfurous synthesis in cancer cells, inhibitors of this enzyme have anticancer activity, making fatty acid synthase an attractive drug target for anti-cancer therapy.
Multi-enzymes: the ultimate organic chemists
Mammalian fatty acerbic synthase belongs to a large fellowship of multi-enzymes, some of which are responsible for the deductive reasoning of complex natural products with antibiotic, anti-cancer, antimycotic agent and immunosuppressor properties that are of outstanding medical relevance. The structure of mammalian fat person acid synthase reveals how different catalytic domains are excised or inserted in various members of this family to yield multi-enzymes capable of synthesizing a large variety of chemical products. The structure will facilitate the design of molecular assemblage lines for the production of improved compounds. In particular, the engineering of novel multi-enzymes for the production of modified antibiotics is important in the fight against resistant strains of bacteria.
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Tuesday, 9 September 2008
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