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2px6

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2px6, resolution 2.30Å ()
Ligands: ,
Gene: FAS (Homo sapiens)
Activity: Fatty-acid synthase, with EC number 2.3.1.85
Domains: Thioesterase
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Contents

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

Publication Abstract from PubMed

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.

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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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 2 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  • Pemble CW 4th, Johnson LC, Kridel SJ, Lowther WT. Crystal structure of the thioesterase domain of human fatty acid synthase inhibited by Orlistat. Nat Struct Mol Biol. 2007 Aug;14(8):704-9. Epub 2007 Jul 8. PMID:17618296 doi:10.1038/nsmb1265

Page seeded by OCA on Tue Feb 17 08:41:30 2009

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