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| | <StructureSection load='2we6' size='340' side='right'caption='[[2we6]], [[Resolution|resolution]] 2.42Å' scene=''> | | <StructureSection load='2we6' size='340' side='right'caption='[[2we6]], [[Resolution|resolution]] 2.42Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2we6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plafa Plafa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WE6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WE6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2we6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WE6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WE6 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2wdt|2wdt]]</div></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]] 2.42Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2we6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2we6 OCA], [https://pdbe.org/2we6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2we6 RCSB], [https://www.ebi.ac.uk/pdbsum/2we6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2we6 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=2we6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2we6 OCA], [https://pdbe.org/2we6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2we6 RCSB], [https://www.ebi.ac.uk/pdbsum/2we6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2we6 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/UCHL3_PLAF7 UCHL3_PLAF7] Thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8 (PubMed:17371404, PubMed:31658303, PubMed:20042598). Essential for parasite blood stage survival (PubMed:20042598).<ref>PMID:17371404</ref> <ref>PMID:20042598</ref> <ref>PMID:31658303</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Plafa]] | + | [[Category: Plasmodium falciparum]] |
| - | [[Category: Ubiquitinyl hydrolase 1]]
| + | [[Category: Artavanis-Tsakonas K]] |
| - | [[Category: Artavanis-Tsakonas, K]] | + | [[Category: Gaudet R]] |
| - | [[Category: Gaudet, R]] | + | [[Category: Ploegh HL]] |
| - | [[Category: Ploegh, H L]] | + | [[Category: Weihofen WA]] |
| - | [[Category: Weihofen, W A]] | + | |
| - | [[Category: Cystein proteinase]]
| + | |
| - | [[Category: Deneddylating enzyme]]
| + | |
| - | [[Category: Deubiquitinating enzyme]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Peptidase_c12]]
| + | |
| - | [[Category: Ubiquitin isopeptidase]]
| + | |
| - | [[Category: Uch-l superfamily]]
| + | |
| Structural highlights
Function
UCHL3_PLAF7 Thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8 (PubMed:17371404, PubMed:31658303, PubMed:20042598). Essential for parasite blood stage survival (PubMed:20042598).[1] [2] [3]
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
Like their human hosts, Plasmodium falciparum parasites rely on the ubiquitin-proteasome system for survival. We previously identified PfUCHL3, a deubiquitinating enzyme, and here we characterize its activity and changes in active site architecture upon binding to ubiquitin. We find strong evidence that PfUCHL3 is essential to parasite survival. The crystal structures of both PfUCHL3 alone and in complex with the ubiquitin-based suicide substrate UbVME suggest a rather rigid active site crossover loop that likely plays a role in restricting the size of ubiquitin adduct substrates. Molecular dynamics simulations of the structures and a model of the PfUCHL3-PfNedd8 complex allowed the identification of shared key interactions of ubiquitin and PfNedd8 with PfUCHL3, explaining the dual specificity of this enzyme. Distinct differences observed in ubiquitin binding between PfUCHL3 and its human counterpart make it likely that the parasitic DUB can be selectively targeted while leaving the human enzyme unaffected.
Characterization and structural studies of the Plasmodium falciparum ubiquitin and Nedd8 hydrolase UCHL3.,Artavanis-Tsakonas K, Weihofen WA, Antos JM, Coleman BI, Comeaux CA, Duraisingh MT, Gaudet R, Ploegh HL J Biol Chem. 2010 Feb 26;285(9):6857-66. Epub 2009 Dec 30. PMID:20042598[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Frickel EM, Quesada V, Muething L, Gubbels MJ, Spooner E, Ploegh H, Artavanis-Tsakonas K. Apicomplexan UCHL3 retains dual specificity for ubiquitin and Nedd8 throughout evolution. Cell Microbiol. 2007 Jun;9(6):1601-10. PMID:17371404 doi:10.1111/j.1462-5822.2007.00896.x
- ↑ Artavanis-Tsakonas K, Weihofen WA, Antos JM, Coleman BI, Comeaux CA, Duraisingh MT, Gaudet R, Ploegh HL. Characterization and structural studies of the Plasmodium falciparum ubiquitin and Nedd8 hydrolase UCHL3. J Biol Chem. 2010 Feb 26;285(9):6857-66. Epub 2009 Dec 30. PMID:20042598 doi:10.1074/jbc.M109.072405
- ↑ Karpiyevich M, Adjalley S, Mol M, Ascher DB, Mason B, van der Heden van Noort GJ, Laman H, Ovaa H, Lee MCS, Artavanis-Tsakonas K. Nedd8 hydrolysis by UCH proteases in Plasmodium parasites. PLoS Pathog. 2019 Oct 28;15(10):e1008086. PMID:31658303 doi:10.1371/journal.ppat.1008086
- ↑ Artavanis-Tsakonas K, Weihofen WA, Antos JM, Coleman BI, Comeaux CA, Duraisingh MT, Gaudet R, Ploegh HL. Characterization and structural studies of the Plasmodium falciparum ubiquitin and Nedd8 hydrolase UCHL3. J Biol Chem. 2010 Feb 26;285(9):6857-66. Epub 2009 Dec 30. PMID:20042598 doi:10.1074/jbc.M109.072405
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