8bdm
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==VCB in complex with compound 26== | |
| + | <StructureSection load='8bdm' size='340' side='right'caption='[[8bdm]], [[Resolution|resolution]] 2.02Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8bdm]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BDM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BDM FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene>, <scene name='pdbligand=QE9:(2~{S},4~{R})-~{N}-[[2-(2-methoxyethoxy)-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-1-[(2~{R})-3-methyl-2-(3-methyl-1,2-oxazol-5-yl)butanoyl]-4-oxidanyl-pyrrolidine-2-carboxamide'>QE9</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=8bdm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bdm OCA], [https://pdbe.org/8bdm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bdm RCSB], [https://www.ebi.ac.uk/pdbsum/8bdm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bdm ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ELOB_HUMAN ELOB_HUMAN] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).<ref>PMID:7638163</ref> <ref>PMID:15590694</ref> The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.<ref>PMID:7638163</ref> <ref>PMID:15590694</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Herein, we describe a systematic SAR- and SPR-investigation of the peptidomimetic hydroxy-proline based VHL-ligand VH032, from which most to-date published VHL-targeting PROTACs have been derived. This study provides for the first time a consistent data set which allows for direct comparison of structural variations including those which were so far hidden in patent literature. The gained knowledge about improved VHL binders was used to design a small library of highly potent BRD4-degraders comprising different VHL exit vectors. Newly designed degraders showed favorable molecular properties and significantly improved degradation potency compared to MZ1. | ||
| - | + | Systematic Potency & Property Assessment of VHL Ligands and Implications on PROTAC Design.,Krieger J, Sorell FJ, Wegener AA, Leuthner B, Machrouhi-Porcher F, Hecht M, Leibrock EM, Mueller JE, Eisert J, Hartung IV, Schlesiger S ChemMedChem. 2023 Feb 7. doi: 10.1002/cmdc.202200615. PMID:36749883<ref>PMID:36749883</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8bdm" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Lehmann M]] | ||
| + | [[Category: Mueller JE]] | ||
| + | [[Category: Sorrell FJ]] | ||
| + | [[Category: Wegener A]] | ||
Revision as of 10:26, 15 February 2023
VCB in complex with compound 26
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