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reading 3 - Mammalian fatty acid synthase = multienzyme...

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Mammalian fatty acid synthase = multienzyme that catalyzes all steps of fatty acid synthesis 1 st paragraph: difference between funagal and mammalian FASs in structural organization. Fatty acid biosynthesis involves cyclic decarboxylative condensation of acyl-coenzyme A (CoA) with the elongation substrate malonyl-CoA, initiated by the starter substrate acetyle-CoA. FAS is overexpressed in many cancer/tumor cells. FAS inhibitors demonstrate anti-tumor activity. Structural information for mFAS is limited to high-resolution structures for the isolated MAT and TE domains based on x-ray crystallography. Overall topology: The crystal structures of mFAS (both in free and in complex with the cofactor NADP+) have been determined. 1. Intertwined dimer, x shape 2. Two nonenzymatic domains: a. Pseudo-methyltransferase b. Pseudo-ketoreductase 3. How do two polypeptides contact? a. Hemophilic interactions of KS and ER b. Hemophilic interactions between the DH and the double “hot dog” folds c. C-terminal of the linker region between the MAT and DH with the KS Interdomain linking and interaction: 1. Only 9% of total sequence for mFAS lnkers 2. 16% for the lateral noncatalytic pseudo-ME and pseudo-KR 3. In contrast to fungal FAS, no scaffolding insertions in catalytic core
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This note was uploaded on 10/28/2010 for the course CHEM 157 taught by Professor burkart during the Spring '07 term at UCSD.

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reading 3 - Mammalian fatty acid synthase = multienzyme...

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