3hhd | pdb_00003hhd

Structure of the Human Fatty Acid Synthase KS-MAT Didomain as a Framework for Inhibitor Design.

spinqualitylabelsall models 3hhd, resolution 2.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3hhd is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL Gene: FASN, FAS (HUMAN) Activity: Fatty-acid synthase, with EC number 2.3.1.85 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [FAS_HUMAN] Fatty acid synthetase catalyzes the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH. This multifunctional protein has 7 catalytic activities and an acyl carrier protein. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The human fatty acid synthase (FAS) is a key enzyme in the metabolism of fatty acids and a target for antineoplastic and antiobesity drug development. Due to its size and flexibility, structural studies of mammalian FAS have been limited to individual domains or intermediate-resolution studies of the complete porcine FAS. We describe the high-resolution crystal structure of a large part of human FAS that encompasses the tandem domain of beta-ketoacyl synthase (KS) connected by a linker domain to the malonyltransferase (MAT) domain. Hinge regions that allow for substantial flexibility of the subdomains are defined. The KS domain forms the canonical dimer, and its substrate-binding site geometry differs markedly from that of bacterial homologues but is similar to that of the porcine orthologue. The didomain structure reveals a possible way to generate a small and compact KS domain by omitting a large part of the linker and MAT domains, which could greatly aid in rapid screening of KS inhibitors. In the crystal, the MAT domain exhibits two closed conformations that differ significantly by rigid-body plasticity. This flexibility may be important for catalysis and extends the conformational space previously known for type I FAS and 6-deoxyerythronolide B synthase. Structure of the human fatty acid synthase KS-MAT didomain as a framework for inhibitor design.,Pappenberger G, Benz J, Gsell B, Hennig M, Ruf A, Stihle M, Thoma R, Rudolph MG J Mol Biol. 2010 Mar 26;397(2):508-19. Epub 2010 Feb 2. PMID:20132826 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acyl carrier protein synthase Fatty acid synthase

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