8aoq
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Cereblon isoform 4 from Magnetospirillum gryphiswaldense in complex with compound 20a== | |
| + | <StructureSection load='8aoq' size='340' side='right'caption='[[8aoq]], [[Resolution|resolution]] 2.09Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8aoq]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Magnetospirillum_gryphiswaldense Magnetospirillum gryphiswaldense]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8AOQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8AOQ FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=N8F:(3~{S})-3-(phenylsulfonylmethyl)piperidine-2,6-dione'>N8F</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=8aoq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8aoq OCA], [https://pdbe.org/8aoq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8aoq RCSB], [https://www.ebi.ac.uk/pdbsum/8aoq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8aoq ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/A4TVL0_9PROT A4TVL0_9PROT] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | To expand the chemical toolkit for targeted protein degradation, we report the generation of a new series of non-thalidomide Cereblon (CRBN) ligands. Readily available 2-methylidene glutarimide was converted to a series of 2-((hetero)aryl(methyl))thio glutarimides via the thio-Michael addition reaction. The compounds thus synthesized were evaluated for their affinity to the thalidomide-binding domain of human CRBN and their binding modes studied via X-ray crystallography. This helped identify several promising glutarimide derivatives which bind stronger to CRBN compared to thalidomide and contain a functional group which permits further chemical conjugation. Oxidation of the sulfur atom in a select group of 2-((hetero)aryl(methyl))thio glutarimides produced the respective sulfones which were found to possess a markedly stronger antiproliferative profile against multiple myeloma cell lines and a sophisticated structural binding mode with additional hydrogen bonding interactions. The newly identified Cereblon ligands form the basis for the synthesis of novel PROTAC protein degraders. | ||
| - | + | Synthesis of novel glutarimide ligands for the E3 ligase substrate receptor Cereblon (CRBN): Investigation of their binding mode and antiproliferative effects against myeloma cell lines.,Krasavin M, Adamchik M, Bubyrev A, Heim C, Maiwald S, Zhukovsky D, Zhmurov P, Bunev A, Hartmann MD Eur J Med Chem. 2023 Jan 15;246:114990. doi: 10.1016/j.ejmech.2022.114990. Epub , 2022 Dec 1. PMID:36476642<ref>PMID:36476642</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8aoq" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Magnetospirillum gryphiswaldense]] | ||
| + | [[Category: Hartmann MD]] | ||
| + | [[Category: Heim C]] | ||
| + | [[Category: Maiwald S]] | ||
Revision as of 07:38, 11 January 2023
Cereblon isoform 4 from Magnetospirillum gryphiswaldense in complex with compound 20a
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