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Groundbreaking study on complex movements of enzymes
February 12, 2009A groundbreaking study has revealed in great detail how enzymes in the cell cooperate to make fat. These enzymes are integrated into a single molecular complex known as fatty acid synthase. This complex is regarded as a potential target for developing new anti-obesity and anti-cancer drugs.
Dr. Stuart Smith, at Children's Hospital Oakland Research Institute, collaborated with Drs. Edward Brignole and Francisco Asturias from The Scripps Research Institute in La Jolla, Calif. in a study published in the February 2009 edition of Nature Structural and Molecular Biology and featured on the cover of the journal.
"Fatty Acid Synthase is a remarkably complex structure. It contains all of the components needed to convert carbohydrates into fat," Dr. Smith explained. "We have suspected for some time that the enzyme complex is extremely flexible, which makes it difficult to analyze using X-ray crystallography. Last year the X-ray structure of the complex was solved by a group in Switzerland, but this structure provided only a snapshot of the complex in one of its many poses. We were able to use state-of-the-art electron microscopy to obtain images of the complex in many of its different conformations and assemble these images into a movie that displays the full range of motion of the components of the complex." The results reveal how enzymes that appear distantly located in the X-ray structure are able to make the contacts with each other needed for catalysis. The extraordinary swinging, swiveling and rolling motions of fatty acid synthase are represented on the cover of the journal in the form of a flamenco dancer.
Some pharmaceutical companies are focusing on inhibitors of fatty acid synthase because they are known to block the conversion of carbohydrates into fat and suppress appetite as well as slow the growth of cancer cells. Structural information garnered from X-ray and electron microscope images may aid in the design of more effective inhibitors that could be used therapeutically.
Children's Hospital & Research Center at Oakland
Some pharmaceutical companies are focusing on inhibitors of fatty acid synthase because they are known to block the conversion of carbohydrates into fat and suppress appetite as well as slow the growth of cancer cells. Structural information garnered from X-ray and electron microscope images may aid in the design of more effective inhibitors that could be used therapeutically.
Children's Hospital & Research Center at Oakland
Fatty Acid Synthase Current Events and Fatty Acid Synthase News RSSFood additive may one day help control blood lipids and reduce disease risk
Scientists at Washington University School of Medicine in St. Louis have identified a substance in the liver that helps process fat and glucose. That substance is a component of the common food additive lecithin, and researchers speculate it may one day be possible to use lecithin products to control blood lipids and reduce risk for diabetes, hypertension or cardiovascular disease using treatments delivered in food rather than medication.
Existing anti-obesity drugs may be effective against flu, hepatitis and HIV
Viruses dramatically increase cellular metabolism, and existing anti-obesity drugs may represent a new way to block these metabolic changes and inhibit viral infection, according to a study published today in the journal Nature Biotechnology.
Atomic structure of the mammalian 'fatty acid factory' determined
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.
Hepatitis C virus may need enzyme's help to cause liver disease
A key enzyme may explain how hepatitis C infection causes fatty liver - a buildup of excess fat in the liver, which can lead to life-threatening diseases such as cirrhosis and liver cancer, report University of Pittsburgh Graduate School of Public Health and School of Medicine researchers.
Discovery about obesity drug helping scientists develop new cancer treatments
Based on their surprising discovery that an obesity drug can kill cancer cells, scientists at Wake Forest University School of Medicine have made a new finding about the drug's effects and are working to design more potent cancer treatments.
Potent possibilities for parasite attack
A comparison of three parasite species that cause Leishmaniasis has identified a small number of genes, many new to biology, that will provide a framework to target the search for new treatments.
Obesity drug helps unlock clues about cancer
An approved drug for fighting obesity is helping scientists at Wake Forest University School of Medicine uncover clues about how to stop the growth of cancerous tumors.
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Phylogenetic analysis of homologous fatty acid synthase and polyketide synthase involved in aflatoxin biosynthesis.(Hypothesis): An article from: Bioinformation by Marina Marcet-Houben (Author), Maria Cabre (Author), Jose L. Paternain (Author), Antoni Romeu (Author) This digital document is an article from Bioinformation, published by Biomedical Informatics Publishing Group on January 1, 2008. The length of the article is 3746 words. The page length shown above is based on a typical 300-word page. The article is delivered in HTML format and is available immediately after purchase. You can view it with any web browser. From the author: Keywords: aflatoxin; aflatoxin biosynthesis; HexA/B multienzymatic complex; polyketide synthase; Aspergillus Citation Details Title: Phylogenetic analysis of homologous fatty acid synthase and polyketide synthase involved in aflatoxin biosynthesis.(Hypothesis) Author: Marina Marcet-Houben Publication: Bioinformation (Magazine/Journal) Date: January 1, 2008 Publisher: Biomedical Informatics... | |
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Fatty Acid Synthase: A Novel Target for Antineoplastic Therapy? (Acta Biomedica Lovaniensia) by Ellen De Schrijver (Author) This is a Ph.D. dissertation. Fatty acid synthase (FAS) is a key lipogenic enzyme catalyzing the terminal steps in the synthesis of fatty acids. In the majority of normal tissues, FAS expression is low. In many human cancers, however, including cancer of the prostate, FAS expression and FAS activity are very high. As shown in the laboratory, overexpression of FAS in tumor cells is part of a more general and coordinate upregulation of multiple lipogenic genes caused, at least in part, by activation of sterol regulatory element binding proteins (SREBPs), transcription factors that play a key role in cellular lipid homeostasis. The mechanisms underlying the activation of the SREBP pathway and the increase in lipogenesis in tumor cells as well as the ultimate biological significance of... |
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Science: September 5, 2008; Mammalian Fatty Acid Synthase by AAAS (Publisher) | |
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Characterization of 2 Novel Fatty Acid Dioxygenases: Linoleate Diol Synthase and Manganese Lipoxygenase (Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, 209) by Chao Su (Author) |
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