4v32
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | ''' | + | ==Cereblon isoform 4 from Magnetospirillum gryphiswaldense in complex with Thalidomide, Y101F mutant== |
| + | <StructureSection load='4v32' size='340' side='right' caption='[[4v32]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4v32]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4V32 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4V32 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EF2:S-THALIDOMIDE'>EF2</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4v2y|4v2y]], [[4v2z|4v2z]], [[4v30|4v30]], [[4v31|4v31]]</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4v32 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4v32 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4v32 RCSB], [http://www.ebi.ac.uk/pdbsum/4v32 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Thalidomide and its derivatives lenalidomide and pomalidomide are important anticancer agents but can cause severe birth defects via an interaction with the protein cereblon. The ligand-binding domain of cereblon is found, with a high degree of conservation, in both bacteria and eukaryotes. Using a bacterial model system, we reveal the structural determinants of cereblon substrate recognition, based on a series of high-resolution crystal structures. For the first time, we identify a cellular ligand that is universally present: we show that thalidomide and its derivatives mimic and compete for the binding of uridine, and validate these findings in vivo. The nature of the binding pocket, an aromatic cage of three tryptophan residues, further suggests a role in the recognition of cationic ligands. Our results allow for general evaluation of pharmaceuticals for potential cereblon-dependent teratogenicity. | ||
| - | + | Thalidomide mimics uridine binding to an aromatic cage in cereblon.,Hartmann MD, Boichenko I, Coles M, Zanini F, Lupas AN, Hernandez Alvarez B J Struct Biol. 2014 Nov 4;188(3):225-232. doi: 10.1016/j.jsb.2014.10.010. PMID:25448889<ref>PMID:25448889</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Alvarez, B Hernandez]] | ||
| + | [[Category: Hartmann, M D]] | ||
| + | [[Category: Lupas, A N]] | ||
| + | [[Category: Aromatic cage]] | ||
| + | [[Category: Signaling protein]] | ||
| + | [[Category: Teratogenicity]] | ||
Revision as of 12:35, 17 December 2014
Cereblon isoform 4 from Magnetospirillum gryphiswaldense in complex with Thalidomide, Y101F mutant
| |||||||||||
