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| | <StructureSection load='5k16' size='340' side='right'caption='[[5k16]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='5k16' size='340' side='right'caption='[[5k16]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5k16]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K16 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5K16 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5k16]] is a 2 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=5K16 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K16 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.599Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5k1c|5k1c]], [[5k1a|5k1a]], [[5k1b|5k1b]], [[5k19|5k19]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">USP12, UBH1, USP12L1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5k16 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k16 OCA], [https://pdbe.org/5k16 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k16 RCSB], [https://www.ebi.ac.uk/pdbsum/5k16 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k16 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] </span></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=5k16 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k16 OCA], [http://pdbe.org/5k16 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k16 RCSB], [http://www.ebi.ac.uk/pdbsum/5k16 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k16 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UBP12_HUMAN UBP12_HUMAN]] Deubiquitinating enzyme. Has almost no deubiquitinating activity by itself and requires the interaction with WDR48 to have a high activity. Not involved in deubiquitination of monoubiquitinated FANCD2.<ref>PMID:19075014</ref> | + | [https://www.uniprot.org/uniprot/UBP12_HUMAN UBP12_HUMAN] Deubiquitinating enzyme. Has almost no deubiquitinating activity by itself and requires the interaction with WDR48 to have a high activity. Not involved in deubiquitination of monoubiquitinated FANCD2.<ref>PMID:19075014</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Thioesterase|Thioesterase]] | + | *[[Thioesterase 3D structures|Thioesterase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ubiquitinyl hydrolase 1]] | + | [[Category: D'Andrea AD]] |
| - | [[Category: Andrea, A D.D]]
| + | [[Category: Li H]] |
| - | [[Category: Li, H]] | + | [[Category: Zheng N]] |
| - | [[Category: Zheng, N]] | + | |
| - | [[Category: Deubiquitination]]
| + | |
| - | [[Category: Deubiquitnating enzyme]]
| + | |
| - | [[Category: Dub]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
UBP12_HUMAN Deubiquitinating enzyme. Has almost no deubiquitinating activity by itself and requires the interaction with WDR48 to have a high activity. Not involved in deubiquitination of monoubiquitinated FANCD2.[1]
Publication Abstract from PubMed
Ubiquitin-specific proteases (USPs) constitute the largest family of deubiquitinating enzymes, whose catalytic competency is often modulated by their binding partners through unknown mechanisms. Here we report on a series of crystallographic and biochemical analyses of an evolutionarily conserved deubiquitinase, USP12, which is activated by two beta-propeller proteins, UAF1 and WDR20. Our structures reveal that UAF1 and WDR20 interact with USP12 at two distinct sites far from its catalytic center. Without increasing the substrate affinity of USP12, the two beta-propeller proteins potentiate the enzyme through different allosteric mechanisms. UAF1 docks at the distal end of the USP12 Fingers domain and induces a cascade of structural changes that reach a critical ubiquitin-contacting loop adjacent to the catalytic cleft. By contrast, WDR20 anchors at the base of this loop and remotely modulates the catalytic center of the enzyme. Our results provide a mechanistic example for allosteric activation of USPs by their regulatory partners.
Allosteric Activation of Ubiquitin-Specific Proteases by beta-Propeller Proteins UAF1 and WDR20.,Li H, Lim KS, Kim H, Hinds TR, Jo U, Mao H, Weller CE, Sun J, Chatterjee C, D'Andrea AD, Zheng N Mol Cell. 2016 Jul 21;63(2):249-60. doi: 10.1016/j.molcel.2016.05.031. Epub 2016 , Jun 30. PMID:27373336[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Cohn MA, Kee Y, Haas W, Gygi SP, D'Andrea AD. UAF1 is a subunit of multiple deubiquitinating enzyme complexes. J Biol Chem. 2009 Feb 20;284(8):5343-51. doi: 10.1074/jbc.M808430200. Epub 2008, Dec 15. PMID:19075014 doi:http://dx.doi.org/10.1074/jbc.M808430200
- ↑ Li H, Lim KS, Kim H, Hinds TR, Jo U, Mao H, Weller CE, Sun J, Chatterjee C, D'Andrea AD, Zheng N. Allosteric Activation of Ubiquitin-Specific Proteases by beta-Propeller Proteins UAF1 and WDR20. Mol Cell. 2016 Jul 21;63(2):249-60. doi: 10.1016/j.molcel.2016.05.031. Epub 2016 , Jun 30. PMID:27373336 doi:http://dx.doi.org/10.1016/j.molcel.2016.05.031
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