4n4w

From Proteopedia

(Difference between revisions)

Current revision

Structure of the human smoothened receptor in complex with SANT-1.

Structural highlights

4n4w is a 1 chain structure with sequence from Homo sapiens and Shigella flexneri 5 str. 8401. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.8Å
Ligands:	, , , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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] Q0SXH8_SHIF8

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/4n4w"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4n4w]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Shigella_flexneri_5_str._8401 Shigella flexneri 5 str. 8401]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N4W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4N4W FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=SNT:(E)-N-(4-BENZYLPIPERAZIN-1-YL)-1-(3,5-DIMETHYL-1-PHENYL-1H-PYRAZOL-4-YL)METHANIMINE'>SNT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</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>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=SNT:(E)-N-(4-BENZYLPIPERAZIN-1-YL)-1-(3,5-DIMETHYL-1-PHENYL-1H-PYRAZOL-4-YL)METHANIMINE'>SNT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=4n4w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n4w OCA], [https://pdbe.org/4n4w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4n4w RCSB], [https://www.ebi.ac.uk/pdbsum/4n4w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4n4w ProSAT]</span></td></tr>
 </table>

4n4w

From Proteopedia

Current revision

Structure of the human smoothened receptor in complex with SANT-1.

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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