View source for 6aci


==Crystal structure of EPEC effector NleB in complex with FADD death domain==
<StructureSection load='6aci' size='340' side='right'caption='[[6aci]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6aci]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_O127:H6_str._E2348/69 Escherichia coli O127:H6 str. E2348/69] 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=6ACI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ACI FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.87&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</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=6aci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aci OCA], [https://pdbe.org/6aci PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6aci RCSB], [https://www.ebi.ac.uk/pdbsum/6aci PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6aci ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NLEB1_ECO27 NLEB1_ECO27] Protein-arginine N-acetylglucosaminyltransferase effector that disrupts TNF signaling in infected cells, including NF-kappa-B signaling, apoptosis and necroptosis (PubMed:20126447, PubMed:20485572, PubMed:22144899, PubMed:23955153, PubMed:24025841, PubMed:28138023, PubMed:28522607, PubMed:30979585). Acts by catalyzing the transfer of a single N-acetylglucosamine (GlcNAc) to a conserved arginine residue in the death domain of host proteins FADD, TRADD, FAS, TNFRSF1A/TNFR1, TNFRSF25/DR3 and RIPK1: arginine GlcNAcylation prevents homotypic/heterotypic death domain interactions and assembly of the oligomeric TNF-alpha receptor complex, thereby disrupting TNF signaling (PubMed:23955153, PubMed:24025841, PubMed:26883593, PubMed:28522607, PubMed:28860194, PubMed:30979585). Has preference for host FADD as substrate compared to other death domain-containing proteins (PubMed:28860194). Also acts on host proteins without a death domain: catalyzes arginine GlcNAcylation of HIF1A, thereby regulating host glucose metabolism (PubMed:30125331). Also displays intra-bacterial activity by mediating GlcNAcylation of glutathione synthetase GshB (PubMed:31974499). Catalyzes auto-GlcNAcylation, which is required for activity toward death domain-containing host target proteins (PubMed:32432056). Shows a higher enzymatic activity than NleB2 (PubMed:23955153).<ref>PMID:20126447</ref> <ref>PMID:20485572</ref> <ref>PMID:22144899</ref> <ref>PMID:23955153</ref> <ref>PMID:24025841</ref> <ref>PMID:26883593</ref> <ref>PMID:28138023</ref> <ref>PMID:28522607</ref> <ref>PMID:28860194</ref> <ref>PMID:30125331</ref> <ref>PMID:30979585</ref> <ref>PMID:31974499</ref> <ref>PMID:32432056</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Enteropathogenic E. coli NleB and related type III effectors catalyze arginine GlcNAcylation of death domain (DD) proteins to block host defense, but the underlying mechanism is unknown. Here we solve crystal structures of NleB alone and in complex with FADD-DD, UDP, and Mn(2+) as well as NleB-GlcNAcylated DDs of TRADD and RIPK1. NleB adopts a GT-A fold with a unique helix-pair insertion to hold FADD-DD; the interface contacts explain the selectivity of NleB for certain DDs. The acceptor arginine is fixed into a cleft, in which Glu253 serves as a base to activate the guanidinium. Analyses of the enzyme-substrate complex and the product structures reveal an inverting sugar-transfer reaction and a detailed catalytic mechanism. These structural insights are validated by mutagenesis analyses of NleB-mediated GlcNAcylation in vitro and its function in mouse infection. Our study builds a structural framework for understanding of NleB-catalyzed arginine GlcNAcylation of host death domain.

Structural and Functional Insights into Host Death Domains Inactivation by the Bacterial Arginine GlcNAcyltransferase Effector.,Ding J, Pan X, Du L, Yao Q, Xue J, Yao H, Wang DC, Li S, Shao F Mol Cell. 2019 Apr 3. pii: S1097-2765(19)30232-1. doi:, 10.1016/j.molcel.2019.03.028. PMID:30979585<ref>PMID:30979585</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6aci" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli O127:H6 str. E2348/69]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ding J]]
[[Category: Shao F]]