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3wx1

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Revision as of 07:11, 23 December 2016

Mouse Cereblon thalidomide binding domain, selenomethionine derivative

Structural highlights

3wx1 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Related:	3wx2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CRBN_MOUSE] Component of some DCX (DDB1-CUL4-X-box) E3 protein ligase complex, a complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins and is required for limb outgrowth and expression of the fibroblast growth factor FGF8. In the complex, may act as a substrate receptor. Regulates the assembly and neuronal surface expression of large-conductance calcium-activated potassium channels in brain regions involved in memory and learning via its interaction with KCNT1 (By similarity).

Publication Abstract from PubMed

The Cul4-Rbx1-DDB1-Cereblon E3 ubiquitin ligase complex is the target of thalidomide, lenalidomide and pomalidomide, therapeutically important drugs for multiple myeloma and other B-cell malignancies. These drugs directly bind Cereblon (CRBN) and promote the recruitment of substrates Ikaros (IKZF1) and Aiolos (IKZF3) to the E3 complex, thus leading to substrate ubiquitination and degradation. Here we present the crystal structure of human CRBN bound to DDB1 and the drug lenalidomide. A hydrophobic pocket in the thalidomide-binding domain (TBD) of CRBN accommodates the glutarimide moiety of lenalidomide, whereas the isoindolinone ring is exposed to solvent. We also solved the structures of the mouse TBD in the apo state and with thalidomide or pomalidomide. Site-directed mutagenesis in lentiviral-expression myeloma models showed that key drug-binding residues are critical for antiproliferative effects.

Structure of the human Cereblon-DDB1-lenalidomide complex reveals basis for responsiveness to thalidomide analogs.,Chamberlain PP, Lopez-Girona A, Miller K, Carmel G, Pagarigan B, Chie-Leon B, Rychak E, Corral LG, Ren YJ, Wang M, Riley M, Delker SL, Ito T, Ando H, Mori T, Hirano Y, Handa H, Hakoshima T, Daniel TO, Cathers BE Nat Struct Mol Biol. 2014 Aug 10. doi: 10.1038/nsmb.2874. PMID:25108355^[1]

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

References

↑ Chamberlain PP, Lopez-Girona A, Miller K, Carmel G, Pagarigan B, Chie-Leon B, Rychak E, Corral LG, Ren YJ, Wang M, Riley M, Delker SL, Ito T, Ando H, Mori T, Hirano Y, Handa H, Hakoshima T, Daniel TO, Cathers BE. Structure of the human Cereblon-DDB1-lenalidomide complex reveals basis for responsiveness to thalidomide analogs. Nat Struct Mol Biol. 2014 Aug 10. doi: 10.1038/nsmb.2874. PMID:25108355 doi:http://dx.doi.org/10.1038/nsmb.2874

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/3wx1"

@@ Line 1: / Line 1: @@
 ==Mouse Cereblon thalidomide binding domain, selenomethionine derivative==
 <StructureSection load='3wx1' size='340' side='right' caption='[[3wx1]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3wx2|3wx2]]</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=3wx1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wx1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3wx1 RCSB], [http://www.ebi.ac.uk/pdbsum/3wx1 PDBsum]</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=3wx1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wx1 OCA], [http://pdbe.org/3wx1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3wx1 RCSB], [http://www.ebi.ac.uk/pdbsum/3wx1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3wx1 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3wx1" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

3wx1

From Proteopedia

Revision as of 07:11, 23 December 2016

Mouse Cereblon thalidomide binding domain, selenomethionine derivative

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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