1w6j

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[[Image:1w6j.gif|left|200px]]
 
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==Structure of human OSC in complex with Ro 48-8071==
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The line below this paragraph, containing "STRUCTURE_1w6j", creates the "Structure Box" on the page.
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<StructureSection load='1w6j' size='340' side='right'caption='[[1w6j]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1w6j]] is a 1 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=1W6J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W6J FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.2&#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=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=C14:TETRADECANE'>C14</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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{{STRUCTURE_1w6j| PDB=1w6j | SCENE= }}
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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=1w6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w6j OCA], [https://pdbe.org/1w6j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w6j RCSB], [https://www.ebi.ac.uk/pdbsum/1w6j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w6j ProSAT]</span></td></tr>
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</table>
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'''STRUCTURE OF HUMAN OSC IN COMPLEX WITH RO 48-8071'''
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== Disease ==
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[https://www.uniprot.org/uniprot/LSS_HUMAN LSS_HUMAN] Total early-onset cataract;Alopecia-intellectual disability syndrome;Hypotrichosis simplex. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.
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== Function ==
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==Overview==
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[https://www.uniprot.org/uniprot/LSS_HUMAN LSS_HUMAN] Key enzyme in the cholesterol biosynthesis pathway. Catalyzes the cyclization of (S)-2,3 oxidosqualene to lanosterol, a reaction that forms the sterol nucleus (PubMed:14766201, PubMed:7639730, PubMed:26200341). Through the production of lanosterol may regulate lens protein aggregation and increase transparency (PubMed:26200341).<ref>PMID:14766201</ref> <ref>PMID:26200341</ref> <ref>PMID:7639730</ref>
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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/w6/1w6j_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=1w6j 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 ==
In higher organisms the formation of the steroid scaffold is catalysed exclusively by the membrane-bound oxidosqualene cyclase (OSC; lanosterol synthase). In a highly selective cyclization reaction OSC forms lanosterol with seven chiral centres starting from the linear substrate 2,3-oxidosqualene. Valuable data on the mechanism of the complex cyclization cascade have been collected during the past 50 years using suicide inhibitors, mutagenesis studies and homology modelling. Nevertheless it is still not fully understood how the enzyme catalyses the reaction. Because of the decisive role of OSC in cholesterol biosynthesis it represents a target for the discovery of novel anticholesteraemic drugs that could complement the widely used statins. Here we present two crystal structures of the human membrane protein OSC: the target protein with an inhibitor that showed cholesterol lowering in vivo opens the way for the structure-based design of new OSC inhibitors. The complex with the reaction product lanosterol gives a clear picture of the way in which the enzyme achieves product specificity in this highly exothermic cyclization reaction.
In higher organisms the formation of the steroid scaffold is catalysed exclusively by the membrane-bound oxidosqualene cyclase (OSC; lanosterol synthase). In a highly selective cyclization reaction OSC forms lanosterol with seven chiral centres starting from the linear substrate 2,3-oxidosqualene. Valuable data on the mechanism of the complex cyclization cascade have been collected during the past 50 years using suicide inhibitors, mutagenesis studies and homology modelling. Nevertheless it is still not fully understood how the enzyme catalyses the reaction. Because of the decisive role of OSC in cholesterol biosynthesis it represents a target for the discovery of novel anticholesteraemic drugs that could complement the widely used statins. Here we present two crystal structures of the human membrane protein OSC: the target protein with an inhibitor that showed cholesterol lowering in vivo opens the way for the structure-based design of new OSC inhibitors. The complex with the reaction product lanosterol gives a clear picture of the way in which the enzyme achieves product specificity in this highly exothermic cyclization reaction.
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==About this Structure==
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Insight into steroid scaffold formation from the structure of human oxidosqualene cyclase.,Thoma R, Schulz-Gasch T, D'Arcy B, Benz J, Aebi J, Dehmlow H, Hennig M, Stihle M, Ruf A Nature. 2004 Nov 4;432(7013):118-22. PMID:15525992<ref>PMID:15525992</ref>
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1W6J 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=1W6J 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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Insight into steroid scaffold formation from the structure of human oxidosqualene cyclase., Thoma R, Schulz-Gasch T, D'Arcy B, Benz J, Aebi J, Dehmlow H, Hennig M, Stihle M, Ruf A, Nature. 2004 Nov 4;432(7013):118-22. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15525992 15525992]
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</div>
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<div class="pdbe-citations 1w6j" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Lanosterol synthase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Aebi J]]
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[[Category: Aebi, J.]]
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[[Category: Benz J]]
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[[Category: Arcy, B D.]]
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[[Category: D'Arcy B]]
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[[Category: Benz, J.]]
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[[Category: Dehmlow H]]
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[[Category: Dehmlow, H.]]
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[[Category: Hennig M]]
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[[Category: Hennig, M.]]
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[[Category: Ruf A]]
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[[Category: Ruf, A.]]
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[[Category: Schulz-Gasch T]]
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[[Category: Schulz-Gasch, T.]]
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[[Category: Thoma R]]
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[[Category: Thoma, R.]]
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[[Category: B-octyl-glucoside]]
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[[Category: Cholesterol]]
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[[Category: Cyclase]]
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[[Category: Isomerase]]
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[[Category: Lanosterol]]
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[[Category: Monotopic membrane protein]]
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[[Category: Steroid biosynthesis]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 13:13:25 2008''
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Current revision

Structure of human OSC in complex with Ro 48-8071

PDB ID 1w6j

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