This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
8aoq
From Proteopedia
(Difference between revisions)
| Line 4: | Line 4: | ||
== Structural highlights == | == 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> | <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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.088Å</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> | <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> | </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. | ||
| - | |||
| - | 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> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 8aoq" style="background-color:#fffaf0;"></div> | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Cereblon isoform 4 from Magnetospirillum gryphiswaldense in complex with compound 20a
| |||||||||||
