2wdt

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of Plasmodium falciparum UCHL3 in complex with the suicide inhibitor UbVME

Structural highlights

2wdt is a 4 chain structure with sequence from Homo sapiens and Plasmodium falciparum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.3Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2wdt"

@@ Line 9: / Line 9: @@
 </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>
+[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 ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 15: / Line 15: @@
   <jmolCheckbox>
     <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>
   </jmolCheckbox>

2wdt

From Proteopedia

Current revision

Crystal structure of Plasmodium falciparum UCHL3 in complex with the suicide inhibitor UbVME

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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