2vfj

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[[Image:2vfj.jpg|left|200px]]
 
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{{Structure
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==Structure of the A20 Ovarian Tumour (OTU) domain==
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|PDB= 2vfj |SIZE=350|CAPTION= <scene name='initialview01'>2vfj</scene>, resolution 3.2&Aring;
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<StructureSection load='2vfj' size='340' side='right'caption='[[2vfj]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
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|SITE= <scene name='pdbsite=AC1:So4+Binding+Site+For+Chain+C'>AC1</scene>, <scene name='pdbsite=AC2:So4+Binding+Site+For+Chain+D'>AC2</scene>, <scene name='pdbsite=AC3:So4+Binding+Site+For+Chain+C'>AC3</scene>, <scene name='pdbsite=AC4:So4+Binding+Site+For+Chain+D'>AC4</scene> and <scene name='pdbsite=AC5:Mg+Binding+Site+For+Chain+D'>AC5</scene>
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
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<table><tr><td colspan='2'>[[2vfj]] is a 4 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=2VFJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VFJ FirstGlance]. <br>
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|ACTIVITY= <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>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
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|GENE=
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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|DOMAIN=
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2vfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vfj OCA], [https://pdbe.org/2vfj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vfj RCSB], [https://www.ebi.ac.uk/pdbsum/2vfj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vfj ProSAT]</span></td></tr>
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|RELATEDENTRY=
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2vfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vfj OCA], [http://www.ebi.ac.uk/pdbsum/2vfj PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2vfj RCSB]</span>
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== Function ==
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}}
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[https://www.uniprot.org/uniprot/TNAP3_HUMAN TNAP3_HUMAN] Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. Involved in immune and inflammatory responses signaled by cytokines, such as TNF-alpha and IL-1 beta, or pathogens via Toll-like receptors (TLRs) through terminating NF-kappa-B activity. Essential component of a ubiquitin-editing protein complex, comprising also RNF11, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. In cooperation with TAX1BP1 promotes disassembly of E2-E3 ubiquitin protein ligase complexes in IL-1R and TNFR-1 pathways; affected are at least E3 ligases TRAF6, TRAF2 and BIRC2, and E2 ubiquitin-conjugating enzymes UBE2N and UBE2D3. In cooperation with TAX1BP1 promotes ubiquitination of UBE2N and proteasomal degradation of UBE2N and UBE2D3. Upon TNF stimulation, deubiquitinates 'Lys-63'-polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NF-kappa-B. Deubiquinates TRAF6 probably acting on 'Lys-63'-linked polyubiquitin. Upon T-cell receptor (TCR)-mediated T-cell activation, deubiquitinates 'Lys-63'-polyubiquitin chains on MALT1 thereby mediating disassociation of the CBM (CARD11:BCL10:MALT1) and IKK complexes and preventing sustained IKK activation. Deubiquinates NEMO/IKBKG; the function is facilitated by TNIP1 and leads to inhibition of NF-kappa-B activation. Upon stimulation by bacterial peptidoglycans, probably deubiquitinates RIPK2. Can also inhibit I-kappa-B-kinase (IKK) through a non-catalytic mechanism which involves polyubiquitin; polyubiquitin promotes association with IKBKG and prevents IKK MAP3K7-mediated phosphorylation. Targets TRAF2 for lysosomal degradation. In vitro able to deubiquitinate both 'Lys-48'- and 'Lys-63' polyubiquitin chains. Inhibitor of programmed cell death. Has a role in the function of the lymphoid system.<ref>PMID:8692885</ref> <ref>PMID:9299557</ref> <ref>PMID:9882303</ref> <ref>PMID:14748687</ref> <ref>PMID:15258597</ref> <ref>PMID:16684768</ref> <ref>PMID:18952128</ref> <ref>PMID:19494296</ref> <ref>PMID:22099304</ref> <ref>PMID:17961127</ref> <ref>PMID:18164316</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vf/2vfj_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2vfj ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The NF-kappaB (nuclear factor kappaB) regulator A20 antagonises IKK [IkappaB (inhibitor of kappaB) kinase] activation by modulating Lys63-linked polyubiquitination of cytokine-receptor-associated factors including TRAF2/6 (tumour-necrosis-factor-receptor-associated factor 2/6) and RIP1 (receptor-interacting protein 1). In the present paper we describe the crystal structure of the N-terminal OTU (ovarian tumour) deubiquitinase domain of A20, which differs from other deubiquitinases but shares the minimal catalytic core with otubain-2. Analysis of conserved surface regions allows prediction of ubiquitin-binding sites for the proximal and distal ubiquitin molecules. Structural and biochemical analysis suggests a novel architecture of the catalytic triad, which might be present in a subset of OTU domains including Cezanne and TRABID (TRAF-binding domain). Biochemical analysis shows a preference of the isolated A20 OTU domain for Lys48-linked tetraubiquitin in vitro suggesting that additional specificity factors might be required for the physiological function of A20 in cells.
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'''STRUCTURE OF THE A20 OVARIAN TUMOUR (OTU) DOMAIN'''
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Structure of the A20 OTU domain and mechanistic insights into deubiquitination.,Komander D, Barford D Biochem J. 2008 Jan 1;409(1):77-85. PMID:17961127<ref>PMID:17961127</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2vfj" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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The NF-kappaB (nuclear factor kappaB) regulator A20 antagonises IKK [IkappaB (inhibitor of kappaB) kinase] activation by modulating Lys63-linked polyubiquitination of cytokine-receptor-associated factors including TRAF2/6 (tumour-necrosis-factor-receptor-associated factor 2/6) and RIP1 (receptor-interacting protein 1). In the present paper we describe the crystal structure of the N-terminal OTU (ovarian tumour) deubiquitinase domain of A20, which differs from other deubiquitinases but shares the minimal catalytic core with otubain-2. Analysis of conserved surface regions allows prediction of ubiquitin-binding sites for the proximal and distal ubiquitin molecules. Structural and biochemical analysis suggests a novel architecture of the catalytic triad, which might be present in a subset of OTU domains including Cezanne and TRABID (TRAF-binding domain). Biochemical analysis shows a preference of the isolated A20 OTU domain for Lys48-linked tetraubiquitin in vitro suggesting that additional specificity factors might be required for the physiological function of A20 in cells.
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*[[Tumor necrosis factor 3D structures|Tumor necrosis factor 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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2VFJ is a [[Single protein]] structure of 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=2VFJ OCA].
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__TOC__
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</StructureSection>
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==Reference==
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Structure of the A20 OTU domain and mechanistic insights into deubiquitination., Komander D, Barford D, Biochem J. 2008 Jan 1;409(1):77-85. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17961127 17961127]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Ubiquitinyl hydrolase 1]]
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[[Category: Barford D]]
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[[Category: Barford, D.]]
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[[Category: Komander D]]
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[[Category: Komander, D.]]
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[[Category: apoptosis]]
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[[Category: cysteine protease]]
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[[Category: cytokine signalling]]
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[[Category: cytoplasm]]
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[[Category: deubiquitinating enzyme]]
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[[Category: dna-binding]]
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[[Category: hydrolase]]
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[[Category: lys63- linked]]
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[[Category: metal-binding]]
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[[Category: nf-kb]]
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[[Category: nucleus]]
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[[Category: otu]]
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[[Category: ovarian tumour]]
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[[Category: phosphorylation]]
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[[Category: polymorphism]]
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[[Category: protease]]
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[[Category: thiol protease]]
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[[Category: ubiquitin]]
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[[Category: ubl conjugation pathway]]
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[[Category: zinc]]
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[[Category: zinc-finger]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:11:34 2008''
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Current revision

Structure of the A20 Ovarian Tumour (OTU) domain

PDB ID 2vfj

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