2px6: Difference between revisions

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==Overview==

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.

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.

==Disease==

Known diseases associated with this structure: Autoimmune lymphoproliferative syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134637 134637]], Autoimmune lymphoproliferative syndrome, type IA OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134637 134637]], Squamous cell carcinoma, burn scar-related, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134637 134637]]

==About this Structure==

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[[Category: Homo sapiens]]

[[Category: Single protein]]

[[Category: IV, C.W.Pemble.]]

[[Category: IV, C W.Pemble.]]

[[Category: Johnson, L.C.]]

[[Category: Johnson, L C.]]

[[Category: Kridel, S.J.]]

[[Category: Kridel, S J.]]

[[Category: Lowther, W.T.]]

[[Category: Lowther, W T.]]

[[Category: DH9]]

[[Category: DTT]]

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[[Category: thioesaterse domain]]

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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:33:53 2008''

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@@ Line 4: / Line 4: @@
 ==Overview==
-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.
+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.
+==Disease==
+Known diseases associated with this structure: Autoimmune lymphoproliferative syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134637 134637]], Autoimmune lymphoproliferative syndrome, type IA OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134637 134637]], Squamous cell carcinoma, burn scar-related, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134637 134637]]
 ==About this Structure==
@@ Line 14: / Line 17: @@
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
-[[Category: IV, C.W.Pemble.]]
+[[Category: IV, C W.Pemble.]]
-[[Category: Johnson, L.C.]]
+[[Category: Johnson, L C.]]
-[[Category: Kridel, S.J.]]
+[[Category: Kridel, S J.]]
-[[Category: Lowther, W.T.]]
+[[Category: Lowther, W T.]]
 [[Category: DH9]]
 [[Category: DTT]]
@@ Line 26: / Line 29: @@
 [[Category: thioesaterse domain]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:08:39 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:33:53 2008''