3n3k: Difference between revisions

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-[[Image:3n3k.png|left|200px]]
-{{STRUCTURE_3n3k|  PDB=3n3k  |  SCENE=  }}
+==The catalytic domain of USP8 in complex with a USP8 specific inhibitor==
+<StructureSection load='3n3k' size='340' side='right'caption='[[3n3k]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3n3k]] 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=3N3K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3N3K 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]] 2.6&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=3n3k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n3k OCA], [https://pdbe.org/3n3k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3n3k RCSB], [https://www.ebi.ac.uk/pdbsum/3n3k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3n3k ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/UBP8_HUMAN UBP8_HUMAN] Hydrolase that can remove conjugated ubiquitin from proteins and therefore plays an important regulatory role at the level of protein turnover by preventing degradation. Converts both 'Lys-48' an 'Lys-63'-linked ubiquitin chains. Catalytic activity is enhanced in the M phase. Involved in cell proliferation. Required to enter into S phase in response to serum stimulation. May regulate T-cell anergy mediated by RNF128 via the formation of a complex containing RNF128 and OTUB1. Probably regulates the stability of STAM2 and RASGRF1. Regulates endosomal ubiquitin dynamics, cargo sorting, membrane traffic at early endosomes, and maintenance of ESCRT-0 stability. The level of protein ubiquitination on endosomes is essential for maintaining the morphology of the organelle. Deubiquitinates EPS15 and controles tyrosine kinase stability. Removes conjugated ubiquitin from EGFR thus regulating EGFR degradation and downstream MAPK signaling. Involved in acrosome biogenesis through interaction with the spermatid ESCRT-0 complex and microtubules. Deubiquitinates BIRC6/bruce and KIF23/MKLP1.<ref>PMID:9628861</ref> <ref>PMID:16520378</ref> <ref>PMID:17711858</ref> <ref>PMID:18329369</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n3/3n3k_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3n3k ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The ubiquitin system regulates virtually all aspects of cellular function. We report a method to target the myriad enzymes that govern ubiquitination of protein substrates. We used massively diverse combinatorial libraries of ubiquitin variants to develop inhibitors of four deubiquitinases (DUBs) and analyzed the DUB-inhibitor complexes with crystallography. We extended the selection strategy to the ubiquitin conjugating (E2) and ubiquitin ligase (E3) enzymes and found that ubiquitin variants can also enhance enzyme activity. Last, we showed that ubiquitin variants can bind selectively to ubiquitin-binding domains. Ubiquitin variants exhibit selective function in cells and thus enable orthogonal modulation of specific enzymatic steps in the ubiquitin system.
-===The catalytic domain of USP8 in complex with a USP8 specific inhibitor===
+A strategy for modulation of enzymes in the ubiquitin system.,Ernst A, Avvakumov G, Tong J, Fan Y, Zhao Y, Alberts P, Persaud A, Walker JR, Neculai AM, Neculai D, Vorobyov A, Garg P, Beatty L, Chan PK, Juang YC, Landry MC, Yeh C, Zeqiraj E, Karamboulas K, Allali-Hassani A, Vedadi M, Tyers M, Moffat J, Sicheri F, Pelletier L, Durocher D, Raught B, Rotin D, Yang J, Moran MF, Dhe-Paganon S, Sidhu SS Science. 2013 Feb 1;339(6119):590-5. doi: 10.1126/science.1230161. Epub 2013 Jan , 3. PMID:23287719<ref>PMID:23287719</ref>
-{{ABSTRACT_PUBMED_17035239}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 3n3k" style="background-color:#fffaf0;"></div>
-[[3n3k]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N3K OCA].
 ==See Also==
-*[[Ubiquitin|Ubiquitin]]
+*[[Thioesterase 3D structures|Thioesterase 3D structures]]
+*[[3D structures of ubiquitin|3D structures of ubiquitin]]
-==Reference==
+== References ==
-<ref group="xtra">PMID:017035239</ref><references group="xtra"/>
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Ubiquitin thiolesterase]]
+[[Category: Large Structures]]
-[[Category: Allali-Hassani, A.]]
+[[Category: Allali-Hassani A]]
-[[Category: Arrowsmith, C H.]]
+[[Category: Arrowsmith CH]]
-[[Category: Avvakumov, G V.]]
+[[Category: Avvakumov GV]]
-[[Category: Bochkarev, A.]]
+[[Category: Bochkarev A]]
-[[Category: Bountra, C.]]
+[[Category: Bountra C]]
-[[Category: Consortium, Structural Genomics.]]
+[[Category: Dhe-Paganon S]]
-[[Category: Dhe-Paganon, S.]]
+[[Category: Edwards AM]]
-[[Category: Edwards, A M.]]
+[[Category: Ernst A]]
-[[Category: Ernst, A.]]
+[[Category: Lam R]]
-[[Category: Lam, R.]]
+[[Category: Li Y]]
-[[Category: Li, Y.]]
+[[Category: Sidhu S]]
-[[Category: Sidhu, S.]]
-[[Category: Walker, J R.]]
-[[Category: Weigelt, J.]]
-[[Category: Xue, S.]]
-[[Category: Deubiquitinating enzyme]]
-[[Category: Dub]]
-[[Category: Hydrolase]]
-[[Category: Inhibitor]]
-[[Category: Isopeptide bond]]
-[[Category: Nucleus]]
-[[Category: Phosphoprotein]]
-[[Category: Protease]]
-[[Category: Sgc]]
 [[Category: Structural genomic]]
-[[Category: Structural genomics consortium]]
+[[Category: Walker JR]]
-[[Category: Thiol protease]]
+[[Category: Weigelt J]]
-[[Category: Ubiquitin]]
+[[Category: Xue S]]
-[[Category: Ubl conjugation pathway]]
-[[Category: Zinc ribbon]]