8aop
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8aop]] 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=8AOP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8AOP FirstGlance]. <br> | <table><tr><td colspan='2'>[[8aop]] 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=8AOP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8AOP FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MW6:(3S)-3-[(3-aminophenyl)sulfanylmethyl]piperidine-2,6-dione'>MW6</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 1.944Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MW6:(3S)-3-[(3-aminophenyl)sulfanylmethyl]piperidine-2,6-dione'>MW6</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=8aop FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8aop OCA], [https://pdbe.org/8aop PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8aop RCSB], [https://www.ebi.ac.uk/pdbsum/8aop PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8aop ProSAT]</span></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=8aop FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8aop OCA], [https://pdbe.org/8aop PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8aop RCSB], [https://www.ebi.ac.uk/pdbsum/8aop PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8aop ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/A4TVL0_9PROT A4TVL0_9PROT] | [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. | ||
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| - | 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> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 8aop" style="background-color:#fffaf0;"></div> | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Cereblon isoform 4 from Magnetospirillum gryphiswaldense in complex with compound 14r
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