4qin

From Proteopedia

(Difference between revisions)

Revision as of 11:31, 15 February 2023

Structure of the human smoothened receptor in complex with SAG1.5

Structural highlights

4qin is a 1 chain structure with sequence from Escherichia coli and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

C562_ECOLX Electron-transport protein of unknown function.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.^[1]

Publication Abstract from PubMed

The Smoothened receptor (SMO) mediates signal transduction in the hedgehog pathway, which is implicated in normal development and carcinogenesis. SMO antagonists can suppress the growth of some tumours; however, mutations at SMO have been found to abolish their antitumour effects, a phenomenon known as chemoresistance. Here we report three crystal structures of human SMO bound to the antagonists SANT1 and Anta XV, and the agonist, SAG1.5, at 2.6-2.8 A resolution. The long and narrow cavity in the transmembrane domain of SMO harbours multiple ligand binding sites, where SANT1 binds at a deeper site as compared with other ligands. Distinct interactions at D473(6.54f) elucidated the structural basis for the differential effects of chemoresistance mutations on SMO antagonists. The agonist SAG1.5 induces a conformational rearrangement of the binding pocket residues, which could contribute to SMO activation. Collectively, these studies reveal the structural basis for the modulation of SMO by small molecules.

Structural basis for Smoothened receptor modulation and chemoresistance to anticancer drugs.,Wang C, Wu H, Evron T, Vardy E, Han GW, Huang XP, Hufeisen SJ, Mangano TJ, Urban DJ, Katritch V, Cherezov V, Caron MG, Roth BL, Stevens RC Nat Commun. 2014 Jul 10;5:4355. doi: 10.1038/ncomms5355. PMID:25008467^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Endoh-Yamagami S, Evangelista M, Wilson D, Wen X, Theunissen JW, Phamluong K, Davis M, Scales SJ, Solloway MJ, de Sauvage FJ, Peterson AS. The mammalian Cos2 homolog Kif7 plays an essential role in modulating Hh signal transduction during development. Curr Biol. 2009 Aug 11;19(15):1320-6. doi: 10.1016/j.cub.2009.06.046. Epub 2009, Jul 9. PMID:19592253 doi:http://dx.doi.org/10.1016/j.cub.2009.06.046
↑ Wang C, Wu H, Evron T, Vardy E, Han GW, Huang XP, Hufeisen SJ, Mangano TJ, Urban DJ, Katritch V, Cherezov V, Caron MG, Roth BL, Stevens RC. Structural basis for Smoothened receptor modulation and chemoresistance to anticancer drugs. Nat Commun. 2014 Jul 10;5:4355. doi: 10.1038/ncomms5355. PMID:25008467 doi:http://dx.doi.org/10.1038/ncomms5355

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4qin"

@@ Line 3: / Line 3: @@
 <StructureSection load='4qin' size='340' side='right'caption='[[4qin]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4qin]] is a 1 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=4QIN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QIN FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4qin]] is a 1 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=4QIN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QIN FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SG8:3-CHLORO-4,7-DIFLUORO-N-[TRANS-4-(METHYLAMINO)CYCLOHEXYL]-N-[3-(PYRIDIN-4-YL)BENZYL]-1-BENZOTHIOPHENE-2-CARBOXAMIDE'>SG8</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SG8:3-CHLORO-4,7-DIFLUORO-N-[TRANS-4-(METHYLAMINO)CYCLOHEXYL]-N-[3-(PYRIDIN-4-YL)BENZYL]-1-BENZOTHIOPHENE-2-CARBOXAMIDE'>SG8</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4o9r|4o9r]], [[4qim|4qim]]</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=4qin FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qin OCA], [https://pdbe.org/4qin PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qin RCSB], [https://www.ebi.ac.uk/pdbsum/4qin PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qin ProSAT]</span></td></tr>
-<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=4qin FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qin OCA], [http://pdbe.org/4qin PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qin RCSB], [http://www.ebi.ac.uk/pdbsum/4qin PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qin ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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.[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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Bacillus coli migula 1895]]
+[[Category: Escherichia coli]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Caron, M G]]
+[[Category: Caron MG]]
-[[Category: Cherezov, V]]
+[[Category: Cherezov V]]
-[[Category: Evron, T]]
+[[Category: Evron T]]
-[[Category: GPCR, GPCR Network]]
+[[Category: Han GW]]
-[[Category: Han, G W]]
+[[Category: Huang X-P]]
-[[Category: Huang, X P]]
+[[Category: Hufeisen SJ]]
-[[Category: Hufeisen, S J]]
+[[Category: Katritch V]]
-[[Category: Katritch, V]]
+[[Category: Mangano TJ]]
-[[Category: Mangano, T J]]
+[[Category: Roth BL]]
-[[Category: Roth, B L]]
+[[Category: Stevens RC]]
-[[Category: Stevens, R C]]
+[[Category: Urban DJ]]
-[[Category: Urban, D J]]
+[[Category: Vardy E]]
-[[Category: Vardy, E]]
+[[Category: Wang C]]
-[[Category: Wang, C]]
+[[Category: Wu H]]
-[[Category: Wu, H]]
-[[Category: Agonist]]
-[[Category: Gpcr]]
-[[Category: Gpcr network]]
-[[Category: Human smoothened receptor]]
-[[Category: Membrane]]
-[[Category: Membrane protein]]
-[[Category: Novel protein engineering]]
-[[Category: Psi-biology]]
-[[Category: Signaling protein]]
-[[Category: Structural genomic]]

4qin

From Proteopedia

Revision as of 11:31, 15 February 2023

Structure of the human smoothened receptor in complex with SAG1.5

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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