View source for 3vja


==Crystal structure of the human squalene synthase==
<StructureSection load='3vja' size='340' side='right'caption='[[3vja]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3vja]] is a 2 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=3VJA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VJA 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]] 1.76&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</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=3vja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vja OCA], [https://pdbe.org/3vja PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vja RCSB], [https://www.ebi.ac.uk/pdbsum/3vja PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vja ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FDFT_HUMAN FDFT_HUMAN] 
<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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3vja" style="background-color:#fffaf0;"></div>

==See Also==
*[[Squalene synthase|Squalene synthase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chang WJ]]
[[Category: Jeng WY]]
[[Category: Liu CI]]
[[Category: Wang AHJ]]