View source for 6r1d


==Cereblon isoform 4 from Magnetospirillum gryphiswaldense in complex with compound 7d, co-crystallized==
<StructureSection load='6r1d' size='340' side='right'caption='[[6r1d]], [[Resolution|resolution]] 1.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6r1d]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Magnetospirillum_gryphiswaldense_MSR-1 Magnetospirillum gryphiswaldense MSR-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R1D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6R1D FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JP5:(phenylmethyl)+~{N}-[(3~{S})-2,5-bis(oxidanylidene)pyrrolidin-3-yl]carbamate'>JP5</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=6r1d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r1d OCA], [https://pdbe.org/6r1d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6r1d RCSB], [https://www.ebi.ac.uk/pdbsum/6r1d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6r1d ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A4TVL0_9PROT A4TVL0_9PROT] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Targeted protein degradation via cereblon (CRBN), a substrate receptor of an E3 ubiquitin ligase complex, is an increasingly important strategy in various clinical settings, in which the substrate specificity of CRBN is altered via the binding of small-molecule effectors. To date, such effectors are derived from thalidomide and confer a broad substrate spectrum that is far from being fully characterized. Here, we employed a rational and modular approach to design novel and minimalistic CRBN effectors. In this approach, we took advantage of the binding modes of hydrolyzed metabolites of several thalidomide-derived effectors, which we elucidated via crystallography. These yielded key insights for the optimization of the minimal core binding moiety and its linkage to a chemical moiety that imparts substrate specificity. Based on this scaffold, we present a first active de-novo CRBN effector that is able to degrade the neo-substrate IKZF3 in the cell culture.

De-Novo Design of Cereblon (CRBN) Effectors Guided by Natural Hydrolysis Products of Thalidomide Derivatives.,Heim C, Pliatsika D, Mousavizadeh F, Bar K, Hernandez Alvarez B, Giannis A, Hartmann MD J Med Chem. 2019 Jul 25;62(14):6615-6629. doi: 10.1021/acs.jmedchem.9b00454. Epub, 2019 Jul 12. PMID:31251063<ref>PMID:31251063</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6r1d" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Magnetospirillum gryphiswaldense MSR-1]]
[[Category: Hartmann MD]]
[[Category: Heim C]]