View source for 13iv


==E. coli DaK bound to peptide PA1, structure A==
<StructureSection load='13iv' size='340' side='right'caption='[[13iv]], [[Resolution|resolution]] 3.23&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[13iv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=13IV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=13IV 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]] 3.23&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1DFX:1-[(2S)-2-cyclohexyl-2-({(2S)-2-cyclohexyl-2-[(pyrazine-2-carbonyl)amino]acetyl}amino)acetyl]-L-prolyl-L-norvalyl-L-phenylalanine'>A1DFX</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=13iv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=13iv OCA], [https://pdbe.org/13iv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=13iv RCSB], [https://www.ebi.ac.uk/pdbsum/13iv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=13iv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DNAK_ECO57 DNAK_ECO57] Acts as a chaperone.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The heat shock protein 70 (Hsp70) family consists of ATP-driven molecular chaperones essential for maintaining protein homeostasis (proteostasis) across all cell types, however, modulation of chaperone activity by small molecules remains challenging. In bacteria, a major Hsp70 called DnaK represents a putative antibacterial target, as it plays essential roles in growth, antibiotic resistance, and stress response. While Hsp70 inhibitors are in development as potential cancer and neurodegenerative disease treatments in humans, we lack generalizable methods to target Hsp70s across species. Here, we address how peptidomimetic scaffolds designed to inhibit proteases, exemplified by the drug telaprevir, interact with two different bacterial DnaKs to disrupt chaperone function. We perform extensive structure-function studies of telaprevir analogs against DnaK to inform the design of synthetic unnatural peptide sequences with a range of inhibitory potencies. X-ray crystallography analysis of telaprevir and several synthetic peptidomimetics reveal interactions with DnaK's substrate binding domain via ligand side chain recognition reminiscent of that observed in protease active sites, but in two orientations. These co-complexes inspire the synthesis of shorter peptidomimetics capable of allosterically inhibiting DnaK's ATPase activity. Overall, this work demonstrates that chemical scaffolds devised for protease inhibition may be modified to disrupt Hsp70 chaperone activities.

Reengineering Protease Inhibitors to Disrupt Hsp70 Chaperone Function.,Richards A, Ariza-Mateos A, Ghosh A, Kim M, Sandler S, Yardumian I, Yawson G, Baryza J, Serganov A, Lupoli TJ Angew Chem Int Ed Engl. 2026 May 19:e1777033. doi: 10.1002/anie.1777033. PMID:42154608<ref>PMID:42154608</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 13iv" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Ariza-Mateos A]]
[[Category: Serganov A]]