View source for 7pjk


==Cereblon isoform 4 from Magnetospirillum gryphiswaldense in complex with a benzotriazole analog of thalidomide==
<StructureSection load='7pjk' size='340' side='right'caption='[[7pjk]], [[Resolution|resolution]] 1.99&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7pjk]] is a 3 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=7PJK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PJK 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]] 1.99&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7SE:(3S)-3-(benzotriazol-2-yl)piperidine-2,6-dione'>7SE</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=7pjk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pjk OCA], [https://pdbe.org/7pjk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pjk RCSB], [https://www.ebi.ac.uk/pdbsum/7pjk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pjk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A4TVL0_9PROT A4TVL0_9PROT] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The advent of proteolysis-targeting chimaeras (PROTACs) mandates that new ligands for the recruitment of E3 ligases are discovered. The traditional immunomodulatory drugs (IMiDs) such as thalidomide and its analogues (all based on the phthalimide glutarimide core) bind to Cereblon, the substrate receptor of the CRL4A(CRBN) E3 ligase. We designed a thalidomide analogue in which the phthalimide moiety was replaced with benzotriazole, using an innovative synthesis strategy. Compared to thalidomide, the resulting "benzotriazolo thalidomide" has a similar binding mode, but improved properties, as revealed in crystallographic analyses, affinity assays and cell culture.

Replacing the phthalimide core in thalidomide with benzotriazole.,Krasavin M, Bubyrev A, Kazantsev A, Heim C, Maiwald S, Zhukovsky D, Dar'in D, Hartmann MD, Bunev A J Enzyme Inhib Med Chem. 2022 Dec;37(1):527-530. doi:, 10.1080/14756366.2021.2024525. PMID:35220840<ref>PMID:35220840</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7pjk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Magnetospirillum gryphiswaldense MSR-1]]
[[Category: Hartmann MD]]
[[Category: Heim C]]
[[Category: Maiwald S]]