View source for 5whv


==Crystal structure of ArtB==
<StructureSection load='5whv' size='340' side='right'caption='[[5whv]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5whv]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Salmonella_enterica_subsp._enterica_serovar_Typhimurium_str._DT104 Salmonella enterica subsp. enterica serovar Typhimurium str. DT104]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WHV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WHV 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]] 2.303&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=5whv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5whv OCA], [https://pdbe.org/5whv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5whv RCSB], [https://www.ebi.ac.uk/pdbsum/5whv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5whv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q404H3_SALTM Q404H3_SALTM] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The evolution of virulence traits is central for the emergence or re-emergence of microbial pathogens and for their adaptation to a specific host 1-5 . Typhoid toxin is an essential virulence factor of the human-adapted bacterial pathogen Salmonella Typhi 6,7 , the cause of typhoid fever in humans 8-12 . Typhoid toxin has a unique A2B5 architecture with two covalently linked enzymatic 'A' subunits, PltA and CdtB, associated with a homopentameric 'B' subunit made up of PltB, which has binding specificity for the N-acetylneuraminic acid (Neu5Ac) sialoglycans 6,13 predominantly present in humans 14 . Here, we examine the functional and structural relationship between typhoid toxin and ArtAB, an evolutionarily related AB5 toxin encoded by the broad-host Salmonella Typhimurium 15 . We find that ArtA and ArtB, homologues of PltA and PltB, can form a functional complex with the typhoid toxin CdtB subunit after substitution of a single amino acid in ArtA, while ArtB can form a functional complex with wild-type PltA and CdtB. We also found that, after addition of a single-terminal Cys residue, a CdtB homologue from cytolethal distending toxin can form a functional complex with ArtA and ArtB. In line with the broad host specificity of S. Typhimurium, we found that ArtB binds human glycans, terminated in N-acetylneuraminic acid, as well as glycans terminated in N-glycolylneuraminic acid (Neu5Gc), which are expressed in most other mammals 14 . The atomic structure of ArtB bound to its receptor shows the presence of an additional glycan-binding site, which broadens its binding specificity. Despite equivalent toxicity in vitro, we found that the ArtB/PltA/CdtB chimaeric toxin exhibits reduced lethality in an animal model, indicating that the host specialization of typhoid toxin has optimized its targeting mechanisms to the human host. This is a remarkable example of a toxin evolving to broaden its enzymatic activities and adapt to a specific host.Structural illumination of host glycan interaction in the evolution and host adaptation of the Salmonella typhoid toxin.

Evolution of host adaptation in the Salmonella typhoid toxin.,Gao X, Deng L, Stack G, Yu H, Chen X, Naito-Matsui Y, Varki A, Galan JE Nat Microbiol. 2017 Oct 9. doi: 10.1038/s41564-017-0033-2. PMID:28993610<ref>PMID:28993610</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5whv" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Salmonella enterica subsp. enterica serovar Typhimurium str. DT104]]
[[Category: Galan JE]]
[[Category: Gao X]]