View source for 2zy1


==Crystal structure of the C(30) carotenoid dehydrosqualene synthase from Staphylococcus aureus complexed with bisphosphonate BPH-830==
<StructureSection load='2zy1' size='340' side='right'caption='[[2zy1]], [[Resolution|resolution]] 1.78&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2zy1]] is a 1 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=2ZY1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZY1 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]] 1.78&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=830:DIPOTASSIUM+(2-OXO-2-{[3-(3-PHENOXYPHENYL)PROPYL]AMINO}ETHYL)PHOSPHONATE'>830</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=2zy1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zy1 OCA], [https://pdbe.org/2zy1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zy1 RCSB], [https://www.ebi.ac.uk/pdbsum/2zy1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zy1 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CRTM_STAAU CRTM_STAAU] 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zy/2zy1_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2zy1 ConSurf].
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== Publication Abstract from PubMed ==
The gold color of Staphylococcus aureus is derived from the carotenoid staphyloxanthin, a virulence factor for the organism. Here, we report the synthesis and activity of a broad variety of staphyloxanthin biosynthesis inhibitors that inhibit the first committed step in its biosynthesis, condensation of two farnesyl diphosphate (FPP) molecules to dehydrosqualene, catalyzed by the enzyme dehydrosqualene synthase (CrtM). The most active compounds are phosphonoacetamides that have low nanomolar K(i) values for CrtM inhibition and are active in whole bacterial cells and in mice, where they inhibit S. aureus disease progression. We also report the X-ray crystallographic structure of the most active compound, N-3-(3-phenoxyphenyl)propylphosphonoacetamide (IC(50) = 8 nM, in cells), bound to CrtM. The structure exhibits a complex network of hydrogen bonds between the polar headgroup and the protein, while the 3-phenoxyphenyl side chain is located in a hydrophobic pocket previously reported to bind farnesyl thiodiphosphate (FsPP), as well as biphenyl phosphonosulfonate inhibitors. Given the good enzymatic, whole cell, and in vivo pharmacologic activities, these results should help guide the further development of novel antivirulence factor-based therapies for S. aureus infections.

Inhibition of staphyloxanthin virulence factor biosynthesis in Staphylococcus aureus: in vitro, in vivo, and crystallographic results.,Song Y, Liu CI, Lin FY, No JH, Hensler M, Liu YL, Jeng WY, Low J, Liu GY, Nizet V, Wang AH, Oldfield E J Med Chem. 2009 Jul 9;52(13):3869-80. PMID:19456099<ref>PMID:19456099</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2zy1" style="background-color:#fffaf0;"></div>

==See Also==
*[[Squalene synthase|Squalene synthase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Staphylococcus aureus]]
[[Category: Jeng WY]]
[[Category: Liu CI]]
[[Category: Oldfield E]]
[[Category: Wang AHJ]]