6rop
From Proteopedia
(Difference between revisions)
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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. 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:// | + | <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> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5my0|5my0]], [[5my2|5my2]]</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | + | <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'>[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. | [[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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:31811668</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6rop" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| + | [[Category: Lk3 transgenic mice]] | ||
[[Category: Grininger, M]] | [[Category: Grininger, M]] | ||
[[Category: Paithankar, K S]] | [[Category: Paithankar, K S]] | ||
Revision as of 10:37, 17 June 2020
KS-MAT DI-DOMAIN OF MOUSE FAS WITH OCTANOYL COA
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