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| | <StructureSection load='4bvu' size='340' side='right'caption='[[4bvu]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='4bvu' size='340' side='right'caption='[[4bvu]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4bvu]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/"shigella_paradysenteriae"_weldin_1927 "shigella paradysenteriae" weldin 1927] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BVU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BVU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4bvu]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Shigella_flexneri Shigella flexneri]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BVU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BVU FirstGlance]. <br> |
| - | </td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitin--protein_ligase Ubiquitin--protein ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.19 6.3.2.19] </span></td></tr> | + | </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=4bvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bvu OCA], [https://pdbe.org/4bvu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bvu RCSB], [https://www.ebi.ac.uk/pdbsum/4bvu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bvu ProSAT]</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=4bvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bvu OCA], [http://pdbe.org/4bvu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bvu RCSB], [http://www.ebi.ac.uk/pdbsum/4bvu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bvu ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/OSPG_SHIFL OSPG_SHIFL]] Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protein is a kinase that is involved in down-regulation of the host innate response induced by invasive bacteria. Prevents or at least delays host phospho-NF-kappa-B inhibitor alpha (NFKBIA) degradation. Does not phosphorylate E2 enzymes.<ref>PMID:16162672</ref> [[http://www.uniprot.org/uniprot/UBC_HUMAN UBC_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> [[http://www.uniprot.org/uniprot/UB2D3_HUMAN UB2D3_HUMAN]] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'-, as well as 'Lys-48'-linked polyubiquitination. Cooperates with the E2 CDC34 and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation. Acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin. Ubiquitin chain elongation is then performed by CDC34, building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. Acts also as an initiator E2, in conjunction with RNF8, for the priming of PCNA. Monoubiquitination of PCNA, and its subsequent polyubiquitination, are essential events in the operation of the DNA damage tolerance (DDT) pathway that is activated after DNA damage caused by UV or chemical agents during S-phase. Associates with the BRCA1/BARD1 E3 ligase complex to perform ubiquitination at DNA damage sites following ionizing radiation leading to DNA repair. Targets DAPK3 for ubiquitination which influences promyelocytic leukemia protein nuclear body (PML-NB) formation in the nucleus. In conjunction with the MDM2 and TOPORS E3 ligases, functions ubiquitination of p53/TP53. Supports NRDP1-mediated ubiquitination and degradation of ERBB3 and of BRUCE which triggers apoptosis. In conjunction with the CBL E3 ligase, targets EGFR for polyubiquitination at the plasma membrane as well as during its internalization and transport on endosomes. In conjunction with the STUB1 E3 quality control E3 ligase, ubiquitinates unfolded proteins to catalyze their immediate destruction (By similarity).<ref>PMID:10329681</ref> <ref>PMID:11743028</ref> <ref>PMID:12646252</ref> <ref>PMID:15247280</ref> <ref>PMID:15280377</ref> <ref>PMID:15496420</ref> <ref>PMID:16628214</ref> <ref>PMID:18515077</ref> <ref>PMID:18948756</ref> <ref>PMID:18508924</ref> <ref>PMID:18284575</ref> <ref>PMID:20061386</ref> <ref>PMID:20347421</ref> <ref>PMID:21532592</ref> | + | [[https://www.uniprot.org/uniprot/OSPG_SHIFL OSPG_SHIFL]] Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protein is a kinase that is involved in down-regulation of the host innate response induced by invasive bacteria. Prevents or at least delays host phospho-NF-kappa-B inhibitor alpha (NFKBIA) degradation. Does not phosphorylate E2 enzymes.<ref>PMID:16162672</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Pathogenic bacteria introduce effector proteins directly into the cytosol of eukaryotic cells to promote invasion and colonization. OspG, a Shigella spp. effector kinase, plays a role in this process by helping to suppress the host inflammatory response. OspG has been reported to bind host E2 ubiquitin-conjugating enzymes activated with ubiquitin (E2~Ub), a key enzyme complex in ubiquitin transfer pathways. A co-crystal structure of the OspG/UbcH5c~Ub complex reveals that complex formation has important ramifications for the activity of both OspG and the UbcH5c~Ub conjugate. OspG is a minimal kinase domain containing only essential elements required for catalysis. UbcH5c~Ub binding stabilizes an active conformation of the kinase, greatly enhancing OspG kinase activity. In contrast, interaction with OspG stabilizes an extended, less reactive form of UbcH5c~Ub. Recognizing conserved E2 features, OspG can interact with at least ten distinct human E2s~Ub. Mouse oral infection studies indicate that E2~Ub conjugates act as novel regulators of OspG effector kinase function in eukaryotic host cells.
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| - | E2~Ub conjugates regulate the kinase activity of Shigella effector OspG during pathogenesis.,Pruneda JN, Smith FD, Daurie A, Swaney DL, Villen J, Scott JD, Stadnyk AW, Le Trong I, Stenkamp RE, Klevit RE, Rohde JR, Brzovic PS EMBO J. 2014 Jan 20. PMID:24446487<ref>PMID:24446487</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
| + | |
| - | <div class="pdbe-citations 4bvu" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Ubiquitin conjugating enzyme|Ubiquitin conjugating enzyme]] | + | *[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Shigella paradysenteriae weldin 1927]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ubiquitin--protein ligase]] | + | [[Category: Shigella flexneri]] |
| - | [[Category: Brzovic, P S]] | + | [[Category: Brzovic PS]] |
| - | [[Category: Klevit, R E]] | + | [[Category: Klevit RE]] |
| - | [[Category: LeTrong, I]] | + | [[Category: LeTrong I]] |
| - | [[Category: Pruneda, J N]] | + | [[Category: Pruneda JN]] |
| - | [[Category: Stenkamp, R E]] | + | [[Category: Stenkamp RE]] |
| - | [[Category: Kinase]]
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| - | [[Category: Transferase-ligase-protein binding complex]]
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