View source for 1xk9


==Pseudomanas exotoxin A in complex with the PJ34 inhibitor==
<StructureSection load='1xk9' size='340' side='right'caption='[[1xk9]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1xk9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XK9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XK9 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]] 2.1&#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=1xk9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xk9 OCA], [https://pdbe.org/1xk9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xk9 RCSB], [https://www.ebi.ac.uk/pdbsum/1xk9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xk9 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TOXA_PSEAE TOXA_PSEAE] An NAD-dependent ADP-ribosyltransferase (ADPRT). Catalyzes the transfer of the ADP ribosyl moiety of oxidized NAD (NAD(+)) onto eukaryotic elongation factor 2 (eEF-2) thus arresting protein synthesis. Has an LD(50) of 65 ng/ml against the human lung epithelial cell line C38.<ref>PMID:18276581</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The mono-ADPRT (mono-ADP-ribosyltransferase), Pseudomonas aeruginosa ETA (exotoxin A), catalyses the transfer of ADP-ribose from NAD+ to its protein substrate. A series of water-soluble compounds that structurally mimic the nicotinamide moiety of NAD+ was investigated for their inhibition of the catalytic domain of ETA. The importance of an amide locked into a hetero-ring structure and a core hetero-ring system that is planar was a trend evident by the IC50 values. Also, the weaker inhibitors have core ring structures that are less planar and thus more flexible. One of the most potent inhibitors, PJ34, was further characterized and shown to exhibit competitive inhibition with an inhibition constant K(i) of 140 nM. We also report the crystal structure of the catalytic domain of ETA in complex with PJ34, the first example of a mono-ADPRT in complex with an inhibitor. The 2.1 A (1 A=0.1 nm) resolution structure revealed that PJ34 is bound within the nicotinamide-binding pocket and forms stabilizing hydrogen bonds with the main chain of Gly-441 and to the side-chain oxygen of Gln-485, a member of a proposed catalytic loop. Structural comparison of this inhibitor complex with diphtheria toxin (a mono-ADPRT) and with PARPs [poly(ADP-ribose) polymerases] shows similarity of the catalytic residues; however, a loop similar to that found in ETA is present in diphtheria toxin but not in PARP. The present study provides insight into the important features required for inhibitors that mimic NAD+ and their binding to the mono-ADPRT family of toxins.

Structure-function analysis of water-soluble inhibitors of the catalytic domain of exotoxin A from Pseudomonas aeruginosa.,Yates SP, Taylor PL, Jorgensen R, Ferraris D, Zhang J, Andersen GR, Merrill AR Biochem J. 2005 Feb 1;385(Pt 3):667-75. PMID:15458385<ref>PMID:15458385</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1xk9" style="background-color:#fffaf0;"></div>

==See Also==
*[[Exotoxin 3D structures|Exotoxin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa]]
[[Category: Andersen GR]]
[[Category: Ferrraris D]]
[[Category: Joergensen R]]
[[Category: Merrill AR]]
[[Category: Taylor PJ]]
[[Category: Yates SP]]
[[Category: Zhang J]]