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| | <StructureSection load='3znh' size='340' side='right'caption='[[3znh]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='3znh' size='340' side='right'caption='[[3znh]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3znh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cchfi Cchfi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZNH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZNH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3znh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Crimean-Congo_hemorrhagic_fever_virus_strain_IbAr10200 Crimean-Congo hemorrhagic fever virus strain IbAr10200] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZNH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZNH FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=AYE:PROP-2-EN-1-AMINE'>AYE</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='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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AYE:PROP-2-EN-1-AMINE'>AYE</scene></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=3znh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3znh OCA], [https://pdbe.org/3znh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3znh RCSB], [https://www.ebi.ac.uk/pdbsum/3znh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3znh 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=3znh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3znh OCA], [https://pdbe.org/3znh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3znh RCSB], [https://www.ebi.ac.uk/pdbsum/3znh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3znh ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/L_CCHFI L_CCHFI]] Displays RNA-directed RNA polymerase, deubiquitinating and deISGylase activities. RNA-dependent RNA polymerase is responsible for replication and transcription of the viral RNA genome. The deubiquitinating activity cleaves both ubiquitinated and ISGylated products and may therefore regulate ubiquitin and ISG15 dependent innate immunity. [[https://www.uniprot.org/uniprot/UBB_HUMAN UBB_HUMAN]] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.<ref>PMID:16543144</ref> <ref>PMID:19754430</ref>
| + | [https://www.uniprot.org/uniprot/L_CCHFI L_CCHFI] Displays RNA-directed RNA polymerase, deubiquitinating and deISGylase activities. RNA-dependent RNA polymerase is responsible for replication and transcription of the viral RNA genome. The deubiquitinating activity cleaves both ubiquitinated and ISGylated products and may therefore regulate ubiquitin and ISG15 dependent innate immunity. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cchfi]] | + | [[Category: Crimean-Congo hemorrhagic fever virus strain IbAr10200]] |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ubiquitinyl hydrolase 1]]
| + | [[Category: Berlin I]] |
| - | [[Category: Berlin, I]] | + | [[Category: Ekkebus R]] |
| - | [[Category: Ekkebus, R]] | + | [[Category: Goerdayal G]] |
| - | [[Category: Goerdayal, G]] | + | [[Category: Heck AJR]] |
| - | [[Category: Heck, A J.R]] | + | [[Category: Komander D]] |
| - | [[Category: Komander, D]] | + | [[Category: Kulathu Y]] |
| - | [[Category: Kulathu, Y]] | + | [[Category: Neefjes J]] |
| - | [[Category: Neefjes, J]] | + | [[Category: Ovaa H]] |
| - | [[Category: Ovaa, H]] | + | [[Category: Scholten A]] |
| - | [[Category: Scholten, A]] | + | [[Category: DeJong A]] |
| - | [[Category: DeJong, A]] | + | [[Category: VanKasteren SI]] |
| - | [[Category: VanKasteren, S I]] | + | |
| - | [[Category: Deubiquitinase]]
| + | |
| - | [[Category: Hydrolase-signaling protein complex]]
| + | |
| Structural highlights
Function
L_CCHFI Displays RNA-directed RNA polymerase, deubiquitinating and deISGylase activities. RNA-dependent RNA polymerase is responsible for replication and transcription of the viral RNA genome. The deubiquitinating activity cleaves both ubiquitinated and ISGylated products and may therefore regulate ubiquitin and ISG15 dependent innate immunity.
Publication Abstract from PubMed
Active-site directed probes are powerful in studies of enzymatic function. We report an active-site directed probe based on a warhead so far considered unreactive. By replacing the C-terminal carboxylate of ubiquitin (Ub) with an alkyne functionality, a selective reaction with the active-site cysteine residue of de-ubiquitinating enzymes was observed. The resulting product was shown to be a quaternary vinyl thioether, as determined by X-ray crystallography. Proteomic analysis of proteins bound to an immobilized Ub alkyne probe confirmed the selectivity toward de-ubiquitinating enzymes. The observed reactivity is not just restricted to propargylated Ub, as highlighted by the selective reaction between caspase-1 (interleukin converting enzyme) and a propargylated peptide derived from IL-1beta, a caspase-1 substrate.
On Terminal Alkynes That Can React with Active-Site Cysteine Nucleophiles in Proteases.,Ekkebus R, van Kasteren SI, Kulathu Y, Scholten A, Berlin I, Geurink PP, de Jong A, Goerdayal S, Neefjes J, Heck AJ, Komander D, Ovaa H J Am Chem Soc. 2013 Feb 15. PMID:23387960[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ekkebus R, van Kasteren SI, Kulathu Y, Scholten A, Berlin I, Geurink PP, de Jong A, Goerdayal S, Neefjes J, Heck AJ, Komander D, Ovaa H. On Terminal Alkynes That Can React with Active-Site Cysteine Nucleophiles in Proteases. J Am Chem Soc. 2013 Feb 15. PMID:23387960 doi:http://dx.doi.org/10.1021/ja309802n
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