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| | ==Crystal structure of Plasmodium falciparum UCHL3 in complex with the suicide inhibitor UbVME== | | ==Crystal structure of Plasmodium falciparum UCHL3 in complex with the suicide inhibitor UbVME== |
| - | <StructureSection load='2wdt' size='340' side='right' caption='[[2wdt]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='2wdt' size='340' side='right'caption='[[2wdt]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2wdt]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Plafa Plafa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WDT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WDT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2wdt]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WDT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WDT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></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]] 2.3Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=GVE:METHYL+4-AMINOBUTANOATE'>GVE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GVE:METHYL+4-AMINOBUTANOATE'>GVE</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1xqq|1xqq]], [[2jf5|2jf5]], [[2gbj|2gbj]], [[1ubq|1ubq]], [[1zgu|1zgu]], [[2g45|2g45]], [[2gbk|2gbk]], [[2j7q|2j7q]], [[1f9j|1f9j]], [[2bgf|2bgf]], [[1fxt|1fxt]], [[1tbe|1tbe]], [[2ayo|2ayo]], [[1xd3|1xd3]], [[1gjz|1gjz]], [[1ubi|1ubi]], [[1g6j|1g6j]], [[1nbf|1nbf]], [[1sif|1sif]], [[1d3z|1d3z]], [[2w9n|2w9n]], [[1ogw|1ogw]], [[2gbn|2gbn]], [[2gbm|2gbm]], [[1yx5|1yx5]], [[1c3t|1c3t]], [[1q5w|1q5w]], [[1s1q|1s1q]], [[1yx6|1yx6]]</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=2wdt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wdt OCA], [https://pdbe.org/2wdt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wdt RCSB], [https://www.ebi.ac.uk/pdbsum/2wdt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wdt ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></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=2wdt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wdt OCA], [http://pdbe.org/2wdt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wdt RCSB], [http://www.ebi.ac.uk/pdbsum/2wdt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2wdt 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:20042598, PubMed:31658303). 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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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wd/2wdt_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wd/2wdt_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | ==See Also== | | ==See Also== |
| - | *[[Thioesterase|Thioesterase]] | + | *[[Thioesterase 3D structures|Thioesterase 3D structures]] |
| - | *[[Ubiquitin|Ubiquitin]] | + | *[[3D structures of ubiquitin|3D structures of ubiquitin]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Plafa]] | + | [[Category: Large Structures]] |
| - | [[Category: Ubiquitinyl hydrolase 1]] | + | [[Category: Plasmodium falciparum]] |
| - | [[Category: Artavanis-Tsakonas, K]] | + | [[Category: Artavanis-Tsakonas K]] |
| - | [[Category: Gaudet, R]] | + | [[Category: Gaudet R]] |
| - | [[Category: Ploegh, H L]] | + | [[Category: Ploegh HL]] |
| - | [[Category: Weihofen, W A]] | + | [[Category: Weihofen WA]] |
| - | [[Category: Cystein proteinase]]
| + | |
| - | [[Category: Enzyme-ligand complex]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydrolase-protein binding complex]]
| + | |
| - | [[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:20042598, PubMed:31658303). 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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