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| | ==Ube4B U-box domain== | | ==Ube4B U-box domain== |
| - | <StructureSection load='5o75' size='340' side='right' caption='[[5o75]], [[Resolution|resolution]] 1.48Å' scene=''> | + | <StructureSection load='5o75' size='340' side='right'caption='[[5o75]], [[Resolution|resolution]] 1.48Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5o75]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O75 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O75 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5o75]] is a 1 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=5O75 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5O75 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.483Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=5o75 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o75 OCA], [http://pdbe.org/5o75 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o75 RCSB], [http://www.ebi.ac.uk/pdbsum/5o75 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o75 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=5o75 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o75 OCA], [https://pdbe.org/5o75 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5o75 RCSB], [https://www.ebi.ac.uk/pdbsum/5o75 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5o75 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UBE4B_HUMAN UBE4B_HUMAN]] Binds to the ubiquitin moieties of preformed conjugates and catalyzes ubiquitin chain assembly in conjunction with E1, E2, and E3 (By similarity). | + | [https://www.uniprot.org/uniprot/UBE4B_HUMAN UBE4B_HUMAN] Binds to the ubiquitin moieties of preformed conjugates and catalyzes ubiquitin chain assembly in conjunction with E1, E2, and E3 (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: RING-type E3 ubiquitin transferase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Buetow, L]] | + | [[Category: Large Structures]] |
| - | [[Category: Gabrielsen, M]] | + | [[Category: Buetow L]] |
| - | [[Category: Huang, D T]] | + | [[Category: Gabrielsen M]] |
| - | [[Category: Nakasone, M A]]
| + | [[Category: Huang DT]] |
| - | [[Category: E3 u-box]] | + | [[Category: Nakasone MA]] |
| - | [[Category: Ligase]] | + | |
| - | [[Category: Ubiquitin transfer]]
| + | |
| Structural highlights
Function
UBE4B_HUMAN Binds to the ubiquitin moieties of preformed conjugates and catalyzes ubiquitin chain assembly in conjunction with E1, E2, and E3 (By similarity).
Publication Abstract from PubMed
RING and U-box E3 ubiquitin ligases regulate diverse eukaryotic processes and have been implicated in numerous diseases, but targeting these enzymes remains a major challenge. We report the development of three ubiquitin variants (UbVs), each binding selectively to the RING or U-box domain of a distinct E3 ligase: monomeric UBE4B, phosphorylated active CBL, or dimeric XIAP. Structural and biochemical analyses revealed that UbVs specifically inhibited the activity of UBE4B or phosphorylated CBL by blocking the E2 approximately Ub binding site. Surprisingly, the UbV selective for dimeric XIAP formed a dimer to stimulate E3 activity by stabilizing the closed E2 approximately Ub conformation. We further verified the inhibitory and stimulatory functions of UbVs in cells. Our work provides a general strategy to inhibit or activate RING/U-box E3 ligases and provides a resource for the research community to modulate these enzymes.
A General Strategy for Discovery of Inhibitors and Activators of RING and U-box E3 Ligases with Ubiquitin Variants.,Gabrielsen M, Buetow L, Nakasone MA, Ahmed SF, Sibbet GJ, Smith BO, Zhang W, Sidhu SS, Huang DT Mol Cell. 2017 Oct 19;68(2):456-470.e10. doi: 10.1016/j.molcel.2017.09.027. PMID:29053960[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gabrielsen M, Buetow L, Nakasone MA, Ahmed SF, Sibbet GJ, Smith BO, Zhang W, Sidhu SS, Huang DT. A General Strategy for Discovery of Inhibitors and Activators of RING and U-box E3 Ligases with Ubiquitin Variants. Mol Cell. 2017 Oct 19;68(2):456-470.e10. doi: 10.1016/j.molcel.2017.09.027. PMID:29053960 doi:http://dx.doi.org/10.1016/j.molcel.2017.09.027
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