1gsz

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[[Image:1gsz.gif|left|200px]]<br />
 
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<applet load="1gsz" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1gsz, resolution 2.8&Aring;" />
 
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'''CRYSTAL STRUCTURE OF A SQUALENE CYCLASE IN COMPLEX WITH THE POTENTIAL ANTICHOLESTEREMIC DRUG RO48-8071'''<br />
 
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==Overview==
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==Crystal Structure of a Squalene Cyclase in Complex with the Potential Anticholesteremic Drug Ro48-8071==
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Squalene-hopene cyclase (SHC) catalyzes the conversion of squalene into, pentacyclic compounds. It is the prokaryotic counterpart of the eukaryotic, oxidosqualene cyclase (OSC) that catalyzes the steroid scaffold formation., Because of clear sequence homology, SHC can serve as a model for OSC, which is an attractive target for anticholesteremic drugs. We have, established the crystal structure of SHC complexed with Ro48-8071, a, potent inhibitor of OSC and therefore of cholesterol biosynthesis., Ro48-8071 is bound in the active-center cavity of SHC and extends into the, channel that connects the cavity with the membrane. The binding site of, Ro48-8071 is largely identical with the expected site of squalene; it, differs from a previous model based on photoaffinity labeling. The, knowledge ... [[http://ispc.weizmann.ac.il/pmbin/getpm?12031670 (full description)]]
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<StructureSection load='1gsz' size='340' side='right'caption='[[1gsz]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1gsz]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Alicyclobacillus_acidocaldarius Alicyclobacillus acidocaldarius]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GSZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GSZ FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C8E:(HYDROXYETHYLOXY)TRI(ETHYLOXY)OCTANE'>C8E</scene>, <scene name='pdbligand=R71:[4-({6-[ALLYL(METHYL)AMINO]HEXYL}OXY)-2-FLUOROPHENYL](4-BROMOPHENYL)METHANONE'>R71</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1gsz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gsz OCA], [https://pdbe.org/1gsz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gsz RCSB], [https://www.ebi.ac.uk/pdbsum/1gsz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gsz ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/SQHC_ALIAD SQHC_ALIAD] Catalyzes the cyclization of squalene into hopene.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gs/1gsz_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1gsz ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Squalene-hopene cyclase (SHC) catalyzes the conversion of squalene into pentacyclic compounds. It is the prokaryotic counterpart of the eukaryotic oxidosqualene cyclase (OSC) that catalyzes the steroid scaffold formation. Because of clear sequence homology, SHC can serve as a model for OSC, which is an attractive target for anticholesteremic drugs. We have established the crystal structure of SHC complexed with Ro48-8071, a potent inhibitor of OSC and therefore of cholesterol biosynthesis. Ro48-8071 is bound in the active-center cavity of SHC and extends into the channel that connects the cavity with the membrane. The binding site of Ro48-8071 is largely identical with the expected site of squalene; it differs from a previous model based on photoaffinity labeling. The knowledge of the inhibitor binding mode in SHC is likely to help develop more potent inhibitors for OSC.
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==About this Structure==
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Crystal structure of a squalene cyclase in complex with the potential anticholesteremic drug Ro48-8071.,Lenhart A, Weihofen WA, Pleschke AE, Schulz GE Chem Biol. 2002 May;9(5):639-45. PMID:12031670<ref>PMID:12031670</ref>
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1GSZ is a [[http://en.wikipedia.org/wiki/Single_protein Single protein]] structure of sequence from [[http://en.wikipedia.org/wiki/Alicyclobacillus_acidocaldarius Alicyclobacillus acidocaldarius]] with C8E and R71 as [[http://en.wikipedia.org/wiki/ligands ligands]]. Structure known Active Site: C8A. Full crystallographic information is available from [[http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1GSZ OCA]].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Crystal structure of a squalene cyclase in complex with the potential anticholesteremic drug Ro48-8071., Lenhart A, Weihofen WA, Pleschke AE, Schulz GE, Chem Biol. 2002 May;9(5):639-45. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12031670 12031670]
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</div>
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[[Category: Alicyclobacillus acidocaldarius]]
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<div class="pdbe-citations 1gsz" style="background-color:#fffaf0;"></div>
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[[Category: Single protein]]
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[[Category: Lenhart, A.]]
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[[Category: Pleschke, A.E.W.]]
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[[Category: Schulz, G.E.]]
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[[Category: Weihofen, W.A.]]
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[[Category: C8E]]
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[[Category: R71]]
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[[Category: cholesterol biosynthesis]]
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[[Category: inhibitor interactions]]
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[[Category: isomerase]]
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[[Category: monotopic membrane protein]]
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[[Category: oxidosqualene cyclase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Oct 30 15:18:29 2007''
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==See Also==
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*[[Squalene-hopene cyclase|Squalene-hopene cyclase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Alicyclobacillus acidocaldarius]]
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[[Category: Large Structures]]
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[[Category: Lenhart A]]
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[[Category: Pleschke AEW]]
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[[Category: Schulz GE]]
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[[Category: Weihofen WA]]

Current revision

Crystal Structure of a Squalene Cyclase in Complex with the Potential Anticholesteremic Drug Ro48-8071

PDB ID 1gsz

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