Pemble_2007_Nat.Struct.Mol.Biol_14_704

Reference

Title : Crystal structure of the thioesterase domain of human fatty acid synthase inhibited by Orlistat - Pemble_2007_Nat.Struct.Mol.Biol_14_704
Author(s) : Pemble CWt , Johnson LC , Kridel SJ , Lowther WT
Ref : Nat Struct Mol Biol , 14 :704 , 2007
Abstract : 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.
ESTHER : Pemble_2007_Nat.Struct.Mol.Biol_14_704
PubMedSearch : Pemble_2007_Nat.Struct.Mol.Biol_14_704
PubMedID: 17618296
Gene_locus related to this paper: human-FASN

Related information

Gene_locus related to this paper: human-FASN

Citations formats

Pemble CWt, Johnson LC, Kridel SJ, Lowther WT (2007)
Crystal structure of the thioesterase domain of human fatty acid synthase inhibited by Orlistat
Nat Struct Mol Biol 14 :704

Pemble CWt, Johnson LC, Kridel SJ, Lowther WT (2007)
Nat Struct Mol Biol 14 :704