5k1c: Difference between revisions
New page: '''Unreleased structure''' The entry 5k1c is ON HOLD Authors: Li, H., D'Andrea, A.D., Zheng, N. Description: Crystal structure of the UAF1/WDR20/USP12 complex [[Category: Unreleased St... |
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==Crystal structure of the UAF1/WDR20/USP12 complex== | |||
<StructureSection load='5k1c' size='340' side='right'caption='[[5k1c]], [[Resolution|resolution]] 3.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5k1c]] 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=5K1C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K1C 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]] 3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=TAM:TRIS(HYDROXYETHYL)AMINOMETHANE'>TAM</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=5k1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k1c OCA], [https://pdbe.org/5k1c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k1c RCSB], [https://www.ebi.ac.uk/pdbsum/5k1c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k1c ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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;"> | |||
== 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<ref>PMID:27373336</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: D'Andrea | <div class="pdbe-citations 5k1c" style="background-color:#fffaf0;"></div> | ||
[[Category: Li | |||
[[Category: Zheng | ==See Also== | ||
*[[Thioesterase 3D structures|Thioesterase 3D structures]] | |||
*[[WD-repeat protein 3D structures|WD-repeat protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: D'Andrea AD]] | |||
[[Category: Li H]] | |||
[[Category: Zheng N]] | |||
Latest revision as of 22:17, 20 September 2023
Crystal structure of the UAF1/WDR20/USP12 complexCrystal structure of the UAF1/WDR20/USP12 complex
Structural highlights
FunctionUBP12_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 PubMedUbiquitin-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 AlsoReferences
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