13iq: Difference between revisions

Line 1:

~~'''Unreleased structure'''~~

~~The entry~~ 13iq is ~~ON HOLD until sometime~~ in the ~~future~~

==E. coli DnaK bound to Telaprevir==

== Structural highlights ==

<table><tr><td colspan='2'>[[13iq]] is a 1 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=13IQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=13IQ 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]] 1.87Å</td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1DIB:(3~{S},3~{a}~{S},6~{a}~{R})-2-[(2~{S})-2-[[(2~{S})-2-cyclohexyl-2-(pyrazin-2-ylcarbonylamino)ethanoyl]amino]-3,3-dimethyl-butanoyl]-~{N}-[(3~{S})-1-(cyclopropylamino)-1,2-bis(oxidanylidene)hexan-3-yl]-3,3~{a},4,5,6,6~{a}-hexahydro-1~{H}-cyclopenta[c]pyrrole-3-carboxamide'>A1DIB</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=13iq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=13iq OCA], [https://pdbe.org/13iq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=13iq RCSB], [https://www.ebi.ac.uk/pdbsum/13iq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=13iq ProSAT]</span></td></tr>

</table>

== Function ==

[https://www.uniprot.org/uniprot/DNAK_ECO57 DNAK_ECO57] Acts as a chaperone.

== 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.

~~Authors:~~ Ariza-Mateos, A., Serganov, A.

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>

~~Description~~: E. coli ~~DnaK bound to Telaprevir~~

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

[[Category: ~~Unreleased~~ Structures]]

</div>

[[Category: Ariza-Mateos, A]]

[[Category: Serganov, A]]

== References ==

__TOC__

</StructureSection>

[[Category: Escherichia coli]]

[[Category: Large Structures]]

[[Category: Ariza-Mateos A]]

[[Category: Serganov A]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 13iq is ON HOLD  until sometime in the future
+==E. coli DnaK bound to Telaprevir==
+<StructureSection load='13iq' size='340' side='right'caption='[[13iq]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[13iq]] is a 1 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=13IQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=13IQ 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]] 1.87&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1DIB:(3~{S},3~{a}~{S},6~{a}~{R})-2-[(2~{S})-2-[[(2~{S})-2-cyclohexyl-2-(pyrazin-2-ylcarbonylamino)ethanoyl]amino]-3,3-dimethyl-butanoyl]-~{N}-[(3~{S})-1-(cyclopropylamino)-1,2-bis(oxidanylidene)hexan-3-yl]-3,3~{a},4,5,6,6~{a}-hexahydro-1~{H}-cyclopenta[c]pyrrole-3-carboxamide'>A1DIB</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=13iq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=13iq OCA], [https://pdbe.org/13iq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=13iq RCSB], [https://www.ebi.ac.uk/pdbsum/13iq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=13iq 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.
-Authors: Ariza-Mateos, A., Serganov, A.
+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>
-Description: E. coli DnaK bound to Telaprevir
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Ariza-Mateos, A]]
+<div class="pdbe-citations 13iq" style="background-color:#fffaf0;"></div>
-[[Category: Serganov, A]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Escherichia coli]]
+[[Category: Large Structures]]
+[[Category: Ariza-Mateos A]]
+[[Category: Serganov A]]