2q6m: Difference between revisions

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[[Image:2q6m.jpg|left|200px]]<br /><applet load="2q6m" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2q6m, resolution 1.250&Aring;" />
'''Catalytic fragment of Cholix toxin from Vibrio Cholerae in complex with the PJ34 inhibitor'''<br />


==Overview==
==Catalytic fragment of Cholix toxin from Vibrio Cholerae in complex with the PJ34 inhibitor==
The ADP-ribosyltransferases are a class of enzymes that display activity in a variety of bacterial pathogens responsible for causing diseases in plants and animals including those affecting mankind, such as diphtheria, cholera and whooping cough. We report the characterization of a novel toxin from Vibrio cholerae, which we call cholix toxin. The toxin is active against mammalian cells (IC&lt;SUB&gt;50&lt;/SUB&gt; = 4.6 +/- 0.4 ng/mL) and crustaceans (Artemia nauplii LD&lt;SUB&gt;50&lt;/SUB&gt; = 10 +/- 2 microg/mL). Here we show that this toxin is the third member of the diphthamide-specific class of ADP-ribose transferases and that it possesses specific ADP-ribose transferase activity against ribosomal eukaryotic elongation factor 2. We also describe the high-resolution crystal structures of the multi-domain toxin and its catalytic domain at 2.1 and 1.25 A resolution, respectively. The new structural data show that cholix toxin possesses the necessary molecular features required for infection of eukaryotes by receptor-mediated endocytosis, translocation to the host cytoplasm, and inhibition of protein synthesis by specific modification of elongation factor 2. The crystal structures also provide important insight into the structural basis for activation of toxin ADPRT activity. These results indicate that cholix toxin may be an important virulence factor of Vibrio cholerae that likely plays a significant role in the survival of the organism in an aquatic environment.
<StructureSection load='2q6m' size='340' side='right'caption='[[2q6m]], [[Resolution|resolution]] 1.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2q6m]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibrio_cholerae Vibrio cholerae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q6M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q6M 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]] 1.25&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P34:N~2~,N~2~-DIMETHYL-N~1~-(6-OXO-5,6-DIHYDROPHENANTHRIDIN-2-YL)GLYCINAMIDE'>P34</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=2q6m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q6m OCA], [https://pdbe.org/2q6m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q6m RCSB], [https://www.ebi.ac.uk/pdbsum/2q6m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q6m ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CHXA_VIBCL CHXA_VIBCL] An NAD-dependent ADP-ribosyltransferase (ADPRT), it catalyzes the transfer of the ADP-ribosyl moiety of oxidized NAD onto eukaryotic elongation factor 2 (eEF-2) thus arresting protein synthesis. It probably uses the eukaryotic prolow-density lipoprotein receptor-related protein 1 (LRP1) to enter mouse cells, although there seems to be at least one other receptor as well. Is active against mouse fibroblasts, Chinese hamster ovary eEF-2, brine shrimp (Artemia spp. nauplii) and upon expression in S.cerevisiae.<ref>PMID:18276581</ref> <ref>PMID:19793133</ref>


==About this Structure==
==See Also==
2Q6M is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Vibrio_cholerae Vibrio cholerae] with <scene name='pdbligand=P34:'>P34</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Sites: <scene name='pdbsite=AC1:P34+Binding+Site+For+Residue+A+1001'>AC1</scene> and <scene name='pdbsite=AC2:P34+Binding+Site+For+Residue+A+1002'>AC2</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q6M OCA].
*[[Exotoxin 3D structures|Exotoxin 3D structures]]
 
== References ==
==Reference==
<references/>
Cholix toxin, a novel ADP-ribosylating factor from vibrio cholerae., Jorgensen R, Purdy AE, Fieldhouse RJ, Kimber MS, Bartlett DH, Rod Merrill A, J Biol Chem. 2008 Feb 25;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18276581 18276581]
__TOC__
[[Category: Single protein]]
</StructureSection>
[[Category: Large Structures]]
[[Category: Vibrio cholerae]]
[[Category: Vibrio cholerae]]
[[Category: Jorgensen, R.]]
[[Category: Jorgensen R]]
[[Category: Merrill, A R.]]
[[Category: Merrill AR]]
[[Category: P34]]
[[Category: alpha-beta complex]]
[[Category: domain iii (c-terminal catalytic domain)]]
[[Category: toxin]]
 
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Retrieved from "https://proteopedia.org/2q6m"