4hcp: Difference between revisions

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{{STRUCTURE_4hcp|  PDB=4hcp  |  SCENE=  }}
==crystal structure of Burkholderia pseudomallei effector protein chbp in complex with nedd8==
===crystal structure of Burkholderia pseudomallei effector protein chbp in complex with nedd8===
<StructureSection load='4hcp' size='340' side='right' caption='[[4hcp]], [[Resolution|resolution]] 2.52&Aring;' scene=''>
{{ABSTRACT_PUBMED_23175788}}
== Structural highlights ==
<table><tr><td colspan='2'>[[4hcp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Burps Burps] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HCP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HCP FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4hcn|4hcn]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BPSS1385 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=272560 BURPS]), NEDD8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4hcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hcp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hcp RCSB], [http://www.ebi.ac.uk/pdbsum/4hcp PDBsum]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/NEDD8_HUMAN NEDD8_HUMAN]] Ubiquitin-like protein which plays an important role in cell cycle control and embryogenesis. Covalent attachment to its substrates requires prior activation by the E1 complex UBE1C-APPBP1 and linkage to the E2 enzyme UBE2M. Attachment of NEDD8 to cullins activates their associated E3 ubiquitin ligase activity, and thus promotes polyubiquitination and proteasomal degradation of cyclins and other regulatory proteins.<ref>PMID:10318914</ref> <ref>PMID:10597293</ref> <ref>PMID:11953428</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


==Function==
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>
[[http://www.uniprot.org/uniprot/NEDD8_HUMAN NEDD8_HUMAN]] Ubiquitin-like protein which plays an important role in cell cycle control and embryogenesis. Covalent attachment to its substrates requires prior activation by the E1 complex UBE1C-APPBP1 and linkage to the E2 enzyme UBE2M. Attachment of NEDD8 to cullins activates their associated E3 ubiquitin ligase activity, and thus promotes polyubiquitination and proteasomal degradation of cyclins and other regulatory proteins.<ref>PMID:10318914</ref> <ref>PMID:10597293</ref> <ref>PMID:11953428</ref>


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[4hcp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Burps Burps] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HCP OCA].
</div>


==Reference==
==See Also==
<ref group="xtra">PMID:023175788</ref><references group="xtra"/><references/>
*[[NEDD8|NEDD8]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Burps]]
[[Category: Burps]]
[[Category: Human]]
[[Category: Human]]
[[Category: Shao, F.]]
[[Category: Shao, F]]
[[Category: Yao, Q.]]
[[Category: Yao, Q]]
[[Category: Alpha/beta/alpha fold]]
[[Category: Alpha/beta/alpha fold]]
[[Category: Bacterial cytosol]]
[[Category: Bacterial cytosol]]

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