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[[Image:2zcs.jpg|left|200px]]
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{{STRUCTURE_2zcs|  PDB=2zcs  |  SCENE=  }}
'''Crystal structure of the C(30) carotenoid dehydrosqualene synthase from Staphylococcus aureus complexed with bisphosphonate BPH-700'''


==Crystal structure of the C(30) carotenoid dehydrosqualene synthase from Staphylococcus aureus complexed with bisphosphonate BPH-700==
<StructureSection load='2zcs' size='340' side='right'caption='[[2zcs]], [[Resolution|resolution]] 2.03&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2zcs]] 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=2ZCS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZCS 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]] 2.03&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B70:TRIPOTASSIUM+(1R)-4-BIPHENYL-4-YL-1-PHOSPHONATOBUTANE-1-SULFONATE'>B70</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=2zcs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zcs OCA], [https://pdbe.org/2zcs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zcs RCSB], [https://www.ebi.ac.uk/pdbsum/2zcs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zcs 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/zc/2zcs_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=2zcs ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Staphylococcus aureus produces hospital- and community-acquired infections, with methicillin-resistant S. aureus posing a serious public health threat. The golden carotenoid pigment of S. aureus, staphyloxanthin, promotes resistance to reactive oxygen species and host neutrophil-based killing, and early enzymatic steps in staphyloxanthin production resemble those for cholesterol biosynthesis. We determined the crystal structures of S. aureus dehydrosqualene synthase (CrtM) at 1.58 angstrom resolution, finding structural similarity to human squalene synthase (SQS). We screened nine SQS inhibitors and determined the structures of three, bound to CrtM. One, previously tested for cholesterol-lowering activity in humans, blocked staphyloxanthin biosynthesis in vitro (median inhibitory concentration approximately 100 nM), resulting in colorless bacteria with increased susceptibility to killing by human blood and to innate immune clearance in a mouse infection model. This finding represents proof of principle for a virulence factor-based therapy against S. aureus.


==Overview==
A cholesterol biosynthesis inhibitor blocks Staphylococcus aureus virulence.,Liu CI, Liu GY, Song Y, Yin F, Hensler ME, Jeng WY, Nizet V, Wang AH, Oldfield E Science. 2008 Mar 7;319(5868):1391-4. Epub 2008 Feb 14. PMID:18276850<ref>PMID:18276850</ref>
Staphylococcus aureus produces hospital- and community-acquired infections, with methicillin-resistant S. aureus posing a serious public health threat. The golden carotenoid pigment of S. aureus, staphyloxanthin, promotes resistance to reactive oxygen species and host neutrophil-based killing, and early enzymatic steps in staphyloxanthin production resemble those for cholesterol biosynthesis. We determined the crystal structures of S. aureus dehydrosqualene synthase (CrtM) at 1.58 angstrom resolution, finding structural similarity to human squalene synthase (SQS). We screened nine SQS inhibitors and determined the structures of three, bound to CrtM. One, previously tested for cholesterol-lowering activity in humans, blocked staphyloxanthin biosynthesis in vitro (median inhibitory concentration approximately 100 nM), resulting in colorless bacteria with increased susceptibility to killing by human blood and to innate immune clearance in a mouse infection model. This finding represents proof of principle for a virulence factor-based therapy against S. aureus.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2ZCS is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZCS OCA].
</div>
<div class="pdbe-citations 2zcs" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
A cholesterol biosynthesis inhibitor blocks Staphylococcus aureus virulence., Liu CI, Liu GY, Song Y, Yin F, Hensler ME, Jeng WY, Nizet V, Wang AH, Oldfield E, Science. 2008 Mar 7;319(5868):1391-4. Epub 2008 Feb 14. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18276850 18276850]
*[[Squalene synthase|Squalene synthase]]
[[Category: Single protein]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Staphylococcus aureus]]
[[Category: Staphylococcus aureus]]
[[Category: Jeng, W Y.]]
[[Category: Jeng WY]]
[[Category: Liu, C I.]]
[[Category: Liu CI]]
[[Category: Oldfield, E.]]
[[Category: Oldfield E]]
[[Category: Wang, A H.]]
[[Category: Wang AH]]
[[Category: Bisphosphonate]]
[[Category: Carotenoid biosynthesis]]
[[Category: Crtm]]
[[Category: Head-to-head condensation]]
[[Category: Staphyloxanthin biosynthesis]]
[[Category: Transferase]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 20:09:34 2008''
Retrieved from "https://proteopedia.org/2zcs"