1ezf

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[[Image:1ezf.gif|left|200px]]
 
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{{Structure
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==CRYSTAL STRUCTURE OF HUMAN SQUALENE SYNTHASE==
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|PDB= 1ezf |SIZE=350|CAPTION= <scene name='initialview01'>1ezf</scene>, resolution 2.15&Aring;
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<StructureSection load='1ezf' size='340' side='right'caption='[[1ezf]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=IN0:N-{2-[TRANS-7-CHLORO-1-(2,2-DIMETHYL-PROPYL)+-5-NAPHTHALEN-1-YL-2-OXO-1,2,3,5-TETRAHYDRO-BENZO[E]+[1,4]OXAZEPIN-3-YL]-ACETYL}-ASPARTIC+ACID'>IN0</scene>
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<table><tr><td colspan='2'>[[1ezf]] is a 3 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=1EZF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EZF FirstGlance]. <br>
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Squalene_synthase Squalene synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.21 2.5.1.21] </span>
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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]] 2.15&#8491;</td></tr>
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|GENE=
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IN0:N-{2-[TRANS-7-CHLORO-1-(2,2-DIMETHYL-PROPYL)+-5-NAPHTHALEN-1-YL-2-OXO-1,2,3,5-TETRAHYDRO-BENZO[E]+[1,4]OXAZEPIN-3-YL]-ACETYL}-ASPARTIC+ACID'>IN0</scene></td></tr>
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|DOMAIN=
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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=1ezf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ezf OCA], [https://pdbe.org/1ezf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ezf RCSB], [https://www.ebi.ac.uk/pdbsum/1ezf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ezf ProSAT]</span></td></tr>
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|RELATEDENTRY=
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ezf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ezf OCA], [http://www.ebi.ac.uk/pdbsum/1ezf PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ezf RCSB]</span>
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== Function ==
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}}
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[https://www.uniprot.org/uniprot/FDFT_HUMAN FDFT_HUMAN]
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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/ez/1ezf_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=1ezf ConSurf].
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<div style="clear:both"></div>
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'''CRYSTAL STRUCTURE OF HUMAN SQUALENE SYNTHASE'''
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==See Also==
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*[[Squalene synthase|Squalene synthase]]
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__TOC__
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==Overview==
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</StructureSection>
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Squalene synthase catalyzes the biosynthesis of squalene, a key cholesterol precursor, through a reductive dimerization of two farnesyl diphosphate (FPP) molecules. The reaction is unique when compared with those of other FPP-utilizing enzymes and proceeds in two distinct steps, both of which involve the formation of carbocationic reaction intermediates. Because FPP is located at the final branch point in the isoprenoid biosynthesis pathway, its conversion to squalene through the action of squalene synthase represents the first committed step in the formation of cholesterol, making it an attractive target for therapeutic intervention. We have determined, for the first time, the crystal structures of recombinant human squalene synthase complexed with several different inhibitors. The structure shows that SQS is folded as a single domain, with a large channel in the middle of one face. The active sites of the two half-reactions catalyzed by the enzyme are located in the central channel, which is lined on both sides by conserved aspartate and arginine residues, which are known from mutagenesis experiments to be involved in FPP binding. One end of this channel is exposed to solvent, whereas the other end leads to a completely enclosed pocket surrounded by conserved hydrophobic residues. These observations, along with mutagenesis data identifying residues that affect substrate binding and activity, suggest that two molecules of FPP bind at one end of the channel, where the active center of the first half-reaction is located, and then the stable reaction intermediate moves into the deep pocket, where it is sequestered from solvent and the second half-reaction occurs. Five alpha helices surrounding the active center are structurally homologous to the active core in the three other isoprenoid biosynthetic enzymes whose crystal structures are known, even though there is no detectable sequence homology.
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==About this Structure==
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1EZF is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EZF OCA].
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==Reference==
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Crystal structure of human squalene synthase. A key enzyme in cholesterol biosynthesis., Pandit J, Danley DE, Schulte GK, Mazzalupo S, Pauly TA, Hayward CM, Hamanaka ES, Thompson JF, Harwood HJ Jr, J Biol Chem. 2000 Sep 29;275(39):30610-7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10896663 10896663]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Squalene synthase]]
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[[Category: Danley DE]]
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[[Category: Danley, D E.]]
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[[Category: Hamanaka ES]]
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[[Category: Hamanaka, E S.]]
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[[Category: Harwood HJ]]
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[[Category: Harwood, H J.]]
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[[Category: Hayward CM]]
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[[Category: Hayward, C M.]]
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[[Category: Mazzalupo SM]]
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[[Category: Mazzalupo, S M.]]
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[[Category: Pandit J]]
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[[Category: Pandit, J.]]
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[[Category: Pauly TA]]
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[[Category: Pauly, T A.]]
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[[Category: Schulte GK]]
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[[Category: Schulte, G K.]]
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[[Category: Thompson JF]]
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[[Category: Thompson, J F.]]
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[[Category: all alpha-helix]]
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[[Category: isoprenoid synthase fold]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:12:43 2008''
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Current revision

CRYSTAL STRUCTURE OF HUMAN SQUALENE SYNTHASE

PDB ID 1ezf

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