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9nr3
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==CRBN-DDB1 in complex with GLUL-cN== | |
| + | <StructureSection load='9nr3' size='340' side='right'caption='[[9nr3]], [[Resolution|resolution]] 2.93Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9nr3]] is a 3 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=9NR3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9NR3 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.93Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SNN:L-3-AMINOSUCCINIMIDE'>SNN</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=9nr3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9nr3 OCA], [https://pdbe.org/9nr3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9nr3 RCSB], [https://www.ebi.ac.uk/pdbsum/9nr3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9nr3 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/GLNA_HUMAN GLNA_HUMAN] Defects in GLUL are the cause of congenital systemic glutamine deficiency (CSGD) [MIM:[https://omim.org/entry/610015 610015]. CSGD is a rare developmental disorder with severe brain malformation resulting in multi-organ failure and neonatal death. Glutamine is largely absent from affected patients serum, urine and cerebrospinal fluid.<ref>PMID:16267323</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/GLNA_HUMAN GLNA_HUMAN] This enzyme has 2 functions: it catalyzes the production of glutamine and 4-aminobutanoate (gamma-aminobutyric acid, GABA), the latter in a pyridoxal phosphate-independent manner (By similarity). Essential for proliferation of fetal skin fibroblasts.<ref>PMID:18662667</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The E3 ligase substrate adapter cereblon (CRBN), the primary target of clinical agents thalidomide and lenalidomide, recognizes endogenous substrates bearing the C-terminal cyclic imide modification. Although C-terminal cyclic imides can form spontaneously, an enzyme that regulates their formation and thereby promotes a biological pathway connecting substrates to CRBN is unknown. Here we report that protein carboxymethyltransferase (PCMT1) promotes formation of C-terminal cyclic imides on C-terminal asparagine residues of CRBN substrates. PCMT1 and CRBN coregulate the levels of metabolic enzymes including glutamine synthetase and inorganic pyrophosphatase 1 in vitro, in cells and in vivo, and this regulation is associated with the proepileptic phenotype of CRBN knockout mouse models. The discovery of an enzyme that regulates CRBN substrates through the C-terminal cyclic imide reveals a previously unknown biological pathway that is perturbed by thalidomide derivatives and provides a biochemical basis for the connection between multiple biological processes and CRBN. | ||
| - | + | PCMT1 generates the C-terminal cyclic imide degron on CRBN substrates.,Zhao Z, Xu W, Feng EY, Cao S, Hermoso-Lopez A, Pena-Vega P, Lloyd HC, Porter AKD, Guzman M, Zheng N, Woo CM Nat Chem Biol. 2025 Dec 29. doi: 10.1038/s41589-025-02106-9. PMID:41461925<ref>PMID:41461925</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 9nr3" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Cao S]] | ||
| + | [[Category: Zheng N]] | ||
Current revision
CRBN-DDB1 in complex with GLUL-cN
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