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| | <StructureSection load='2bkr' size='340' side='right'caption='[[2bkr]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='2bkr' size='340' side='right'caption='[[2bkr]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2bkr]] 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=2BKR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BKR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2bkr]] 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=2BKR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BKR FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ndd|1ndd]], [[1r4m|1r4m]], [[1r4n|1r4n]], [[1xt9|1xt9]], [[2bkq|2bkq]]</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]] 1.9Å</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=2bkr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bkr OCA], [http://pdbe.org/2bkr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bkr RCSB], [http://www.ebi.ac.uk/pdbsum/2bkr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2bkr 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=2bkr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bkr OCA], [https://pdbe.org/2bkr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bkr RCSB], [https://www.ebi.ac.uk/pdbsum/2bkr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bkr ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SENP8_HUMAN SENP8_HUMAN]] Protease that catalyzes two essential functions in the NEDD8 pathway: processing of full-length NEDD8 to its mature form and deconjugation of NEDD8 from targeted proteins such as cullins or p53.<ref>PMID:12730221</ref> <ref>PMID:12759363</ref> <ref>PMID:12759362</ref> <ref>PMID:15242646</ref> <ref>PMID:15775960</ref> | + | [https://www.uniprot.org/uniprot/SENP8_HUMAN SENP8_HUMAN] Protease that catalyzes two essential functions in the NEDD8 pathway: processing of full-length NEDD8 to its mature form and deconjugation of NEDD8 from targeted proteins such as cullins or p53.<ref>PMID:12730221</ref> <ref>PMID:12759363</ref> <ref>PMID:12759362</ref> <ref>PMID:15242646</ref> <ref>PMID:15775960</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Dong, C]] | + | [[Category: Dong C]] |
| - | [[Category: Hay, R T]] | + | [[Category: Hay RT]] |
| - | [[Category: Liu, H]] | + | [[Category: Liu H]] |
| - | [[Category: Naismith, J H]] | + | [[Category: Naismith JH]] |
| - | [[Category: Shen, L N]] | + | [[Category: Shen LN]] |
| - | [[Category: Xirodimas, D]] | + | [[Category: Xirodimas D]] |
| - | [[Category: Hydrolase]]
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| - | [[Category: Protease]]
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| - | [[Category: Protein-binding-hydrolase complex]]
| + | |
| - | [[Category: Thiol protease]]
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| - | [[Category: Ubiquitin]]
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| - | [[Category: Ubiquitin-hydrolase complex]]
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| - | [[Category: Ubl conjugation pathway]]
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| Structural highlights
Function
SENP8_HUMAN Protease that catalyzes two essential functions in the NEDD8 pathway: processing of full-length NEDD8 to its mature form and deconjugation of NEDD8 from targeted proteins such as cullins or p53.[1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
NEDD8 (neural precursor cell expressed developmentally downregulated gene 8)-specific protease NEDP1 processes preNEDD8 to its mature form and deconjugates NEDD8 from substrates such as p53 and cullins. Although NEDD8 and ubiquitin are highly related in sequence and structure, their attachment to a protein leads to different biological effects. It is therefore critical that NEDP1 discriminates between NEDD8 and ubiquitin, and this requires remarkable precision in molecular recognition. To determine the basis of this specificity, we have determined the crystal structure of NEDP1 in isolation and in a transition state complex with NEDD8. This reveals that NEDP1 is a cysteine protease of the Ulp family. Binding of NEDD8 induces a dramatic conformational change in a flexible loop that swings over the C-terminus of NEDD8 locking it into an extended beta-structure optimal for catalysis. Structural, mutational and biochemical studies have identified key residues involved in molecular recognition. A single-residue difference in the C-terminus of NEDD8 and ubiquitin contributes significantly to the ability of NEDP1 to discriminate between them. In vivo analysis indicates that NEDP1 mutants perturb deNEDDylation of the tumour suppressor p53.
Structural basis of NEDD8 ubiquitin discrimination by the deNEDDylating enzyme NEDP1.,Shen LN, Liu H, Dong C, Xirodimas D, Naismith JH, Hay RT EMBO J. 2005 Apr 6;24(7):1341-51. Epub 2005 Mar 17. PMID:15775960[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mendoza HM, Shen LN, Botting C, Lewis A, Chen J, Ink B, Hay RT. NEDP1, a highly conserved cysteine protease that deNEDDylates Cullins. J Biol Chem. 2003 Jul 11;278(28):25637-43. Epub 2003 May 1. PMID:12730221 doi:http://dx.doi.org/10.1074/jbc.M212948200
- ↑ Wu K, Yamoah K, Dolios G, Gan-Erdene T, Tan P, Chen A, Lee CG, Wei N, Wilkinson KD, Wang R, Pan ZQ. DEN1 is a dual function protease capable of processing the C terminus of Nedd8 and deconjugating hyper-neddylated CUL1. J Biol Chem. 2003 Aug 1;278(31):28882-91. Epub 2003 May 19. PMID:12759363 doi:http://dx.doi.org/10.1074/jbc.M302888200
- ↑ Gan-Erdene T, Nagamalleswari K, Yin L, Wu K, Pan ZQ, Wilkinson KD. Identification and characterization of DEN1, a deneddylase of the ULP family. J Biol Chem. 2003 Aug 1;278(31):28892-900. Epub 2003 May 19. PMID:12759362 doi:http://dx.doi.org/10.1074/jbc.M302890200
- ↑ Xirodimas DP, Saville MK, Bourdon JC, Hay RT, Lane DP. Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activity. Cell. 2004 Jul 9;118(1):83-97. PMID:15242646 doi:http://dx.doi.org/10.1016/j.cell.2004.06.016
- ↑ Shen LN, Liu H, Dong C, Xirodimas D, Naismith JH, Hay RT. Structural basis of NEDD8 ubiquitin discrimination by the deNEDDylating enzyme NEDP1. EMBO J. 2005 Apr 6;24(7):1341-51. Epub 2005 Mar 17. PMID:15775960
- ↑ Shen LN, Liu H, Dong C, Xirodimas D, Naismith JH, Hay RT. Structural basis of NEDD8 ubiquitin discrimination by the deNEDDylating enzyme NEDP1. EMBO J. 2005 Apr 6;24(7):1341-51. Epub 2005 Mar 17. PMID:15775960
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