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| | <StructureSection load='6rop' size='340' side='right'caption='[[6rop]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='6rop' size='340' side='right'caption='[[6rop]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6rop]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ROP OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6ROP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6rop]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ROP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ROP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO8:OCTANOYL-COENZYME+A'>CO8</scene>, <scene name='pdbligand=OCA:OCTANOIC+ACID+(CAPRYLIC+ACID)'>OCA</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]] 2.7Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5my0|5my0]], [[5my2|5my2]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO8:OCTANOYL-COENZYME+A'>CO8</scene>, <scene name='pdbligand=OCA:OCTANOIC+ACID+(CAPRYLIC+ACID)'>OCA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Fasn ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=6rop FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rop OCA], [https://pdbe.org/6rop PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rop RCSB], [https://www.ebi.ac.uk/pdbsum/6rop PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rop ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6rop FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rop OCA], [http://pdbe.org/6rop PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rop RCSB], [http://www.ebi.ac.uk/pdbsum/6rop PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rop ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FAS_MOUSE FAS_MOUSE]] 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_MOUSE FAS_MOUSE] 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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6rop" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6rop" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Fatty acid synthase 3D structures|Fatty acid synthase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Grininger, M]] | + | [[Category: Grininger M]] |
| - | [[Category: Paithankar, K S]] | + | [[Category: Paithankar KS]] |
| - | [[Category: Rittner, A]] | + | [[Category: Rittner A]] |
| - | [[Category: Mouse fatty-acid-synthase ks-mat]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
FAS_MOUSE 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.
Publication Abstract from PubMed
De novo fatty acid biosynthesis in humans is accomplished by a multidomain protein, the Type I fatty acid synthase (FAS). Although ubiquitously expressed in all tissues, fatty acid synthesis is not essential in normal healthy cells due to sufficient supply with fatty acids by the diet. However, FAS is overexpressed in cancer cells and correlates with tumor malignancy, which makes FAS an attractive selective therapeutic target in tumorigenesis. Herein, we present a crystal structure of the condensing part of murine FAS, highly homologous to human FAS, with octanoyl moieties covalently bound to the transferase (MAT-malonyl-/acetyltransferase) and the condensation (KS-beta-ketoacyl synthase) domain. The MAT domain binds the octanoyl moiety in a novel (unique) conformation, which reflects the pronounced conformational dynamics of the substrate-binding site responsible for the MAT substrate promiscuity. In contrast, the KS binding pocket just subtly adapts to the octanoyl moiety upon substrate binding. Besides the rigid domain structure, we found a positive cooperative effect in the substrate binding of the KS domain by a comprehensive enzyme kinetic study. These structural and mechanistic findings contribute significantly to our understanding of the mode of action of FAS and may guide future rational inhibitor designs.
Type I fatty acid synthase trapped in the octanoyl-bound state.,Rittner A, Paithankar KS, Himmler A, Grininger M Protein Sci. 2020 Feb;29(2):589-605. doi: 10.1002/pro.3797. PMID:31811668[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rittner A, Paithankar KS, Himmler A, Grininger M. Type I fatty acid synthase trapped in the octanoyl-bound state. Protein Sci. 2020 Feb;29(2):589-605. doi: 10.1002/pro.3797. PMID:31811668 doi:http://dx.doi.org/10.1002/pro.3797
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