3vje
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of the Y248A mutant of C(30) carotenoid dehydrosqualene synthase from Staphylococcus aureus in complex with zaragozic acid A== | |
| + | <StructureSection load='3vje' size='340' side='right'caption='[[3vje]], [[Resolution|resolution]] 2.12Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3vje]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VJE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VJE FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.12Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZGA:ZARAGOZIC+ACID+A'>ZGA</scene></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=3vje FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vje OCA], [https://pdbe.org/3vje PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vje RCSB], [https://www.ebi.ac.uk/pdbsum/3vje PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vje ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CRTM_STAAU CRTM_STAAU] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:22474324</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 3vje" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Squalene synthase|Squalene synthase]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Staphylococcus aureus]] | ||
| + | [[Category: Chang WJ]] | ||
| + | [[Category: Jeng WY]] | ||
| + | [[Category: Liu CI]] | ||
| + | [[Category: Wang AHJ]] | ||
Current revision
Crystal structure of the Y248A mutant of C(30) carotenoid dehydrosqualene synthase from Staphylococcus aureus in complex with zaragozic acid A
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