|
|
| Line 3: |
Line 3: |
| | <StructureSection load='3hhd' size='340' side='right'caption='[[3hhd]], [[Resolution|resolution]] 2.15Å' scene=''> | | <StructureSection load='3hhd' size='340' side='right'caption='[[3hhd]], [[Resolution|resolution]] 2.15Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3hhd]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HHD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HHD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3hhd]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HHD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HHD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FASN, FAS ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Fatty-acid_synthase Fatty-acid synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.85 2.3.1.85] </span></td></tr>
| + | |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3hhd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hhd OCA], [https://pdbe.org/3hhd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hhd RCSB], [https://www.ebi.ac.uk/pdbsum/3hhd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hhd ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3hhd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hhd OCA], [https://pdbe.org/3hhd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hhd RCSB], [https://www.ebi.ac.uk/pdbsum/3hhd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hhd ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/FAS_HUMAN 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.
| + | [https://www.uniprot.org/uniprot/FAS_HUMAN 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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 38: |
Line 37: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Fatty-acid synthase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Benz, J]] | + | [[Category: Benz J]] |
| - | [[Category: Pappenberger, G M]] | + | [[Category: Pappenberger GM]] |
| - | [[Category: Rudolph, M G]] | + | [[Category: Rudolph MG]] |
| - | [[Category: Thoma, R]] | + | [[Category: Thoma R]] |
| - | [[Category: Acetylation]]
| + | |
| - | [[Category: Cytoplasm]]
| + | |
| - | [[Category: Fatty acid biosynthesis]]
| + | |
| - | [[Category: Fatty acid synthase]]
| + | |
| - | [[Category: Fatty acid synthesis]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Lipid synthesis]]
| + | |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Megasynthase]]
| + | |
| - | [[Category: Multienzyme]]
| + | |
| - | [[Category: Multifunctional enzyme]]
| + | |
| - | [[Category: Nad]]
| + | |
| - | [[Category: Nadp]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Phosphopantetheine]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Pyridoxal phosphate]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Pappenberger G, Benz J, Gsell B, Hennig M, Ruf A, Stihle M, Thoma R, Rudolph MG. Structure of the human fatty acid synthase KS-MAT didomain as a framework for inhibitor design. J Mol Biol. 2010 Mar 26;397(2):508-19. Epub 2010 Feb 2. PMID:20132826 doi:10.1016/j.jmb.2010.01.066
|
