2px6

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{{STRUCTURE_2px6| PDB=2px6 | SCENE= }}
{{STRUCTURE_2px6| PDB=2px6 | SCENE= }}
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'''Crystal structure of the thioesterase domain of human fatty acid synthase inhibited by Orlistat'''
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===Crystal structure of the thioesterase domain of human fatty acid synthase inhibited by Orlistat===
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==Overview==
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Human fatty acid synthase (FAS) is uniquely expressed at high levels in many tumor types. Pharmacological inhibition of FAS therefore represents an important therapeutic opportunity. The drug Orlistat, which has been approved by the US Food and Drug Administration, inhibits FAS, induces tumor cell-specific apoptosis and inhibits the growth of prostate tumor xenografts. We determined the 2.3-A-resolution crystal structure of the thioesterase domain of FAS inhibited by Orlistat. Orlistat was captured in the active sites of two thioesterase molecules as a stable acyl-enzyme intermediate and as the hydrolyzed product. The details of these interactions reveal the molecular basis for inhibition and suggest a mechanism for acyl-chain length discrimination during the FAS catalytic cycle. Our findings provide a foundation for the development of new cancer drugs that target FAS.
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(as it appears on PubMed at http://www.pubmed.gov), where 17618296 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17618296}}
==Disease==
==Disease==
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[[Category: Tetrahydrolipstatin]]
[[Category: Tetrahydrolipstatin]]
[[Category: Thioesaterse domain]]
[[Category: Thioesaterse domain]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 13:56:59 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 12:06:39 2008''

Revision as of 09:06, 28 July 2008

Image:2px6.png

Template:STRUCTURE 2px6

Contents

Crystal structure of the thioesterase domain of human fatty acid synthase inhibited by Orlistat

Template:ABSTRACT PUBMED 17618296

Disease

Known disease associated with this structure: Autoimmune lymphoproliferative syndrome, type IA OMIM:[134637], Squamous cell carcinoma, burn scar-related, somatic OMIM:[134637], Autoimmune lymphoproliferative syndrome OMIM:[134637]

About this Structure

2PX6 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structure of the thioesterase domain of human fatty acid synthase inhibited by Orlistat., Pemble CW 4th, Johnson LC, Kridel SJ, Lowther WT, Nat Struct Mol Biol. 2007 Aug;14(8):704-9. Epub 2007 Jul 8. PMID:17618296

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