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4hcn

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[[Image:4hcn.jpg|left|200px]]
 
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{{STRUCTURE_4hcn| PDB=4hcn | SCENE= }}
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==Crystal structure of Burkholderia pseudomallei effector protein CHBP in complex with ubiquitin==
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<StructureSection load='4hcn' size='340' side='right'caption='[[4hcn]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4hcn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Burkholderia_pseudomallei_K96243 Burkholderia pseudomallei K96243] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HCN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HCN FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4hcn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hcn OCA], [https://pdbe.org/4hcn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hcn RCSB], [https://www.ebi.ac.uk/pdbsum/4hcn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hcn ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CIF_BURPS CIF_BURPS] Protein-glutamine deamidase effector that inhibits the host cell cycle and other key cellular processes such as the actin network and programmed-cell death (PubMed:19308257, PubMed:20688984, PubMed:19225106). Acts by mediating the side chain deamidation of 'Gln-40' of host NEDD8, converting it to glutamate, thereby abolishing the activity of cullin-RING-based E3 ubiquitin-protein ligase complexes (CRL complexes) (PubMed:20688984, PubMed:21903097). Inactivation of CRL complexes prevents ubiquitination and subsequent degradation of the cyclin-dependent kinase inhibitors CDKN1A/p21 and CDKN1B/p27, leading to G1 and G2 cell cycle arrests in host cells (PubMed:19308257). Deamidation of 'Gln-40' of host NEDD8 also triggers macrophage-specific programmed cell death (PubMed:23175788). Also able to catalyze deamidation of 'Gln-40' of host ubiquitin in vitro; however, NEDD8 constitutes the preferred substrate in vivo (PubMed:20688984). Also regulates the host NF-kappa-B signaling via activation of MAPK/ERK cascade: activation of host MAPK/ERK cascade is independent of CRL complexes inhibition, suggesting that Cif has other host protein targets than NEDD8 (PubMed:28166272, PubMed:29848489).<ref>PMID:19225106</ref> <ref>PMID:19308257</ref> <ref>PMID:20688984</ref> <ref>PMID:21903097</ref> <ref>PMID:23175788</ref> <ref>PMID:28166272</ref> <ref>PMID:29848489</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Targeting eukaryotic proteins for deamidation modification is increasingly appreciated as a general bacterial virulence mechanism. Here, we present an atomic view of how a bacterial deamidase effector, cycle-inhibiting factor homolog in Burkholderia pseudomallei (CHBP), recognizes its host targets, ubiquitin (Ub) and Ub-like neural precursor cell expressed, developmentally down-regulated 8 (NEDD8), and catalyzes site-specific deamidation. Crystal structures of CHBP-Ub/NEDD8 complexes show that Ub and NEDD8 are similarly cradled by a large cleft in CHBP with four contacting surfaces. The pattern of Ub/NEDD8 recognition by CHBP resembles that by the E1 activation enzyme, which critically involves the Lys-11 surface in Ub/NEDD8. Close examination of the papain-like catalytic center reveals structural determinants of CHBP being an obligate glutamine deamidase. Molecular-dynamics simulation identifies Gln-31/Glu-31 of Ub/NEDD8 as one key determinant of CHBP substrate preference for NEDD8. Inspired by the idea of using the unique bacterial activity as a tool, we further discover that CHBP-catalyzed NEDD8 deamidation triggers macrophage-specific apoptosis, which predicts a previously unknown macrophage-specific proapoptotic signal that is negatively regulated by neddylation-mediated protein ubiquitination/degradation.
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===Crystal structure of Burkholderia pseudomallei effector protein CHBP in complex with ubiquitin===
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Structural mechanism of ubiquitin and NEDD8 deamidation catalyzed by bacterial effectors that induce macrophage-specific apoptosis.,Yao Q, Cui J, Wang J, Li T, Wan X, Luo T, Gong YN, Xu Y, Huang N, Shao F Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20395-400. doi:, 10.1073/pnas.1210831109. Epub 2012 Nov 21. PMID:23175788<ref>PMID:23175788</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==About this Structure==
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</div>
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[[4hcn]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Burkholderia_pseudomallei_k96243 Burkholderia pseudomallei k96243] and [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_s288c Saccharomyces cerevisiae s288c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HCN OCA].
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<div class="pdbe-citations 4hcn" style="background-color:#fffaf0;"></div>
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[[Category: Burkholderia pseudomallei k96243]]
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== References ==
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[[Category: Saccharomyces cerevisiae s288c]]
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<references/>
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[[Category: Cui, J.]]
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__TOC__
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[[Category: Shao, F.]]
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</StructureSection>
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[[Category: Yao, Q.]]
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[[Category: Burkholderia pseudomallei K96243]]
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[[Category: Zhu, Y.]]
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[[Category: Large Structures]]
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[[Category: Nedd8]]
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[[Category: Saccharomyces cerevisiae S288C]]
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[[Category: Protein binding]]
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[[Category: Cui J]]
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[[Category: Ubiquitin]]
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[[Category: Shao F]]
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[[Category: Ubiquitin/nedd8 deamidase]]
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[[Category: Yao Q]]
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[[Category: Zhu Y]]

Current revision

Crystal structure of Burkholderia pseudomallei effector protein CHBP in complex with ubiquitin

PDB ID 4hcn

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