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4jkv

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==Structure of the human smoothened 7TM receptor in complex with an antitumor agent==
==Structure of the human smoothened 7TM receptor in complex with an antitumor agent==
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<StructureSection load='4jkv' size='340' side='right' caption='[[4jkv]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
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<StructureSection load='4jkv' size='340' side='right'caption='[[4jkv]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4jkv]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JKV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JKV FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4jkv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JKV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JKV FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1KS:4-FLUORO-N-METHYL-N-{1-[4-(1-METHYL-1H-PYRAZOL-5-YL)PHTHALAZIN-1-YL]PIPERIDIN-4-YL}-2-(TRIFLUOROMETHYL)BENZAMIDE'>1KS</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr>
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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]] 2.45&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cybC, SMO_HUMAN, SMO, SMOH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=1KS:4-FLUORO-N-METHYL-N-{1-[4-(1-METHYL-1H-PYRAZOL-5-YL)PHTHALAZIN-1-YL]PIPERIDIN-4-YL}-2-(TRIFLUOROMETHYL)BENZAMIDE'>1KS</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4jkv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jkv OCA], [http://pdbe.org/4jkv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jkv RCSB], [http://www.ebi.ac.uk/pdbsum/4jkv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jkv ProSAT]</span></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=4jkv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jkv OCA], [https://pdbe.org/4jkv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jkv RCSB], [https://www.ebi.ac.uk/pdbsum/4jkv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jkv ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX]] Electron-transport protein of unknown function.
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[https://www.uniprot.org/uniprot/SMO_HUMAN SMO_HUMAN] G protein-coupled receptor that probably associates with the patched protein (PTCH) to transduce the hedgehog's proteins signal. Binding of sonic hedgehog (SHH) to its receptor patched is thought to prevent normal inhibition by patched of smoothened (SMO). Required for the accumulation of KIF7 and GLI3 in the cilia.<ref>PMID:19592253</ref> [https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The smoothened (SMO) receptor, a key signal transducer in the hedgehog signalling pathway, is responsible for the maintenance of normal embryonic development and is implicated in carcinogenesis. It is classified as a class frizzled (class F) G-protein-coupled receptor (GPCR), although the canonical hedgehog signalling pathway involves the GLI transcription factors and the sequence similarity with class A GPCRs is less than 10%. Here we report the crystal structure of the transmembrane domain of the human SMO receptor bound to the small-molecule antagonist LY2940680 at 2.5 A resolution. Although the SMO receptor shares the seven-transmembrane helical fold, most of the conserved motifs for class A GPCRs are absent, and the structure reveals an unusually complex arrangement of long extracellular loops stabilized by four disulphide bonds. The ligand binds at the extracellular end of the seven-transmembrane-helix bundle and forms extensive contacts with the loops.
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Structure of the human smoothened receptor bound to an antitumour agent.,Wang C, Wu H, Katritch V, Han GW, Huang XP, Liu W, Siu FY, Roth BL, Cherezov V, Stevens RC Nature. 2013 May 1. doi: 10.1038/nature12167. PMID:23636324<ref>PMID:23636324</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4jkv" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Bacillus coli migula 1895]]
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[[Category: Escherichia coli]]
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[[Category: Cherezov, V]]
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[[Category: Homo sapiens]]
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[[Category: GPCR, GPCR Network]]
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[[Category: Large Structures]]
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[[Category: Han, G W]]
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[[Category: Cherezov V]]
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[[Category: Huang, X]]
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[[Category: Han GW]]
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[[Category: Katritch, V]]
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[[Category: Huang X]]
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[[Category: Liu, W]]
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[[Category: Katritch V]]
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[[Category: Roth, B L]]
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[[Category: Liu W]]
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[[Category: Siu, F Y]]
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[[Category: Roth BL]]
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[[Category: Stevens, R C]]
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[[Category: Siu FY]]
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[[Category: Wang, C]]
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[[Category: Stevens RC]]
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[[Category: Wu, H]]
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[[Category: Wang C]]
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[[Category: Antitumor agent]]
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[[Category: Wu H]]
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[[Category: Gpcr]]
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[[Category: Gpcr network]]
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[[Category: Human smoothened receptor]]
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[[Category: Membrane]]
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[[Category: Membrane protein]]
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[[Category: Novel protein engineering]]
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[[Category: Psi-biology]]
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[[Category: Structural genomic]]
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Current revision

Structure of the human smoothened 7TM receptor in complex with an antitumor agent

PDB ID 4jkv

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