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| | ==Crystal structure of the human squalene synthase== | | ==Crystal structure of the human squalene synthase== |
| - | <StructureSection load='3vjb' size='340' side='right' caption='[[3vjb]], [[Resolution|resolution]] 2.05Å' scene=''> | + | <StructureSection load='3vjb' size='340' side='right'caption='[[3vjb]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3vjb]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VJB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VJB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3vjb]] is a 6 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=3VJB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VJB FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3vj8|3vj8]], [[3vj9|3vj9]], [[3vja|3vja]], [[3vjc|3vjc]], [[3vjd|3vjd]], [[3vje|3vje]]</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]] 2.05Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FDFT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3vjb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vjb OCA], [https://pdbe.org/3vjb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vjb RCSB], [https://www.ebi.ac.uk/pdbsum/3vjb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vjb ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Squalene_synthase Squalene synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.21 2.5.1.21] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3vjb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vjb OCA], [http://pdbe.org/3vjb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3vjb RCSB], [http://www.ebi.ac.uk/pdbsum/3vjb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3vjb ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/FDFT_HUMAN FDFT_HUMAN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Squalene synthase]] | + | [[Category: Large Structures]] |
| - | [[Category: Chang, W J]] | + | [[Category: Chang WJ]] |
| - | [[Category: Jeng, W Y]] | + | [[Category: Jeng WY]] |
| - | [[Category: Liu, C I]] | + | [[Category: Liu CI]] |
| - | [[Category: Wang, A H.J]] | + | [[Category: Wang AHJ]] |
| - | [[Category: Cholesterol biosynthesis]]
| + | |
| - | [[Category: Farnesyl-diphosphate farnesyltransferase]]
| + | |
| - | [[Category: Head-to-head synthase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
FDFT_HUMAN
Publication Abstract from PubMed
Zaragozic acids (ZAs) belong to a family of fungal metabolites with nanomolar inhibitory activity toward squalene synthase (SQS). The enzyme catalyzes the committed step of sterol synthesis and has attracted attention as a potential target for antilipogenic and antiinfective therapies. Here, we have determined the structure of ZA-A complexed with human SQS. ZA-A binding induces a local conformational change in the substrate binding site, and its C-6 acyl group also extends over to the cofactor binding cavity. In addition, ZA-A effectively inhibits a homologous bacterial enzyme, dehydrosqualene synthase (CrtM), which synthesizes the precursor of staphyloxanthin in Staphylococcus aureus to cope with oxidative stress. Size reduction at Tyr(248) in CrtM further increases the ZA-A binding affinity, and it reveals a similar overall inhibitor binding mode to that of human SQS/ZA-A except for the C-6 acyl group. These structures pave the way for further improving selectivity and development of a new generation of anticholesterolemic and antimicrobial inhibitors.
Binding modes of zaragozic acid A to human squalene synthase and staphylococcal dehydrosqualene synthase.,Liu CI, Jeng WY, Chang WJ, Ko TP, Wang AH J Biol Chem. 2012 May 25;287(22):18750-7. Epub 2012 Apr 3. PMID:22474324[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Liu CI, Jeng WY, Chang WJ, Ko TP, Wang AH. Binding modes of zaragozic acid A to human squalene synthase and staphylococcal dehydrosqualene synthase. J Biol Chem. 2012 May 25;287(22):18750-7. Epub 2012 Apr 3. PMID:22474324 doi:10.1074/jbc.M112.351254
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