View source for 6xrw


==Chromosomal ParDE TA system from P. aeruginosa==
<StructureSection load='6xrw' size='340' side='right'caption='[[6xrw]], [[Resolution|resolution]] 1.77&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6xrw]] is a 4 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=6XRW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XRW 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]] 1.77&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2PE:NONAETHYLENE+GLYCOL'>2PE</scene>, <scene name='pdbligand=BEN:BENZAMIDINE'>BEN</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=6xrw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xrw OCA], [https://pdbe.org/6xrw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xrw RCSB], [https://www.ebi.ac.uk/pdbsum/6xrw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xrw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9I708_PSEAE Q9I708_PSEAE] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Type-II toxin-antitoxin (TA) systems are comprised of two tightly interacting proteins, and operons encoding these systems have been identified throughout the genomes of bacteria. In contrast to secretion system effector-immunity pairs, TA systems must remain paired to protect the host cell from toxicity. Continual depletion of the antitoxin results in a shorter half-life than that of the toxin, though it is unclear if antitoxins can be effectively degraded when complexed with toxins. The current work probed the protein-protein interface of the PaParDE1 TA system, guided by an X-ray crystal structure, to determine contributions of antitoxin amino acids to interaction kinetics and affinity. These studies identified a "hotspot" position that alters the binding mode and resulting affinity (K(D)) from 152 pM for a 1:1 model for wild type to 25.5 and 626 nM for a 2:1 model with mutated antitoxin. This correlates with an altered induced secondary structure upon complexation with PaParE1 and increased kinetics of Lon protease digestion of the antitoxin despite the toxin presence. However, the decreased affinity at this hotspot was essentially reversed when the antitoxin dimerization region was deleted, yielding insights into complex interactions involved in the tight association. Removal of the antitoxin C-terminal seven amino acids, corresponding to the site of a disorder-to-order transition, completely prevents association. These studies combine to provide a model for the initiation of the TA interaction and highlight how manipulation of the sequence can impact the antitoxin disorder-to-order transition, weakening the affinity and resulting in increased antitoxin susceptibility to degradation.

ParD Antitoxin Hotspot Alters a Disorder-to-Order Transition upon Binding to Its Cognate ParE Toxin, Lessening Its Interaction Affinity and Increasing Its Protease Degradation Kinetics.,Snead KJ, Moore LL, Bourne CR Biochemistry. 2022 Jan 4;61(1):34-45. doi: 10.1021/acs.biochem.1c00584. Epub 2021 , Dec 16. PMID:34914378<ref>PMID:34914378</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6xrw" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa]]
[[Category: Bourne CR]]
[[Category: Snead KJ]]
[[Category: Thomas LM]]