View source for 6jjl


==Crystal structure of the DegP dodecamer with a modulator==
<StructureSection load='6jjl' size='340' side='right'caption='[[6jjl]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6jjl]] is a 18 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JJL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JJL 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]] 4.2&#8491;</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=6jjl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jjl OCA], [https://pdbe.org/6jjl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jjl RCSB], [https://www.ebi.ac.uk/pdbsum/6jjl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jjl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DEGP_ECOLI DEGP_ECOLI] DegP acts as a chaperone at low temperatures but switches to a peptidase (heat shock protein) at higher temperatures. It degrades transiently denatured and unfolded proteins which accumulate in the periplasm following heat shock or other stress conditions. DegP is efficient with Val-Xaa and Ile-Xaa peptide bonds, suggesting a preference for beta-branched side chain amino acids. Only unfolded proteins devoid of disulfide bonds appear capable of being cleaved, thereby preventing non-specific proteolysis of folded proteins. Its proteolytic activity is essential for the survival of cells at elevated temperatures. It can degrade IciA, ada, casein, globin and PapA. DegP shares specificity with DegQ. DegP is also involved in the biogenesis of partially folded outer-membrane proteins (OMP).<ref>PMID:2180903</ref> <ref>PMID:8830688</ref> <ref>PMID:10319814</ref> <ref>PMID:18505836</ref> <ref>PMID:12730160</ref> <ref>PMID:18496527</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Rising antibiotic resistance urgently begs for novel targets and strategies for antibiotic discovery. Here, we report that over-activation of the periplasmic DegP protease, a member of the highly conserved HtrA family, can be a viable strategy for antibiotic development. We demonstrate that tripodal peptidyl compounds that mimic DegP-activating lipoprotein variants allosterically activate DegP and inhibit the growth of an Escherichia coli strain with a permeable outer membrane in a DegP-dependent fashion. Interestingly, these compounds inhibit bacterial growth at a temperature at which DegP is not essential for cell viability, mainly by over-proteolysis of newly synthesized proteins. Co-crystal structures show that the peptidyl arms of the compounds bind to the substrate-binding sites of DegP. Overall, our results represent an intriguing example of killing bacteria by activating a non-essential enzyme, and thus expand the scope of antibiotic targets beyond the traditional essential proteins or pathways.

Over-activation of a nonessential bacterial protease DegP as an antibiotic strategy.,Cho H, Choi Y, Min K, Son JB, Park H, Lee HH, Kim S Commun Biol. 2020 Oct 1;3(1):547. doi: 10.1038/s42003-020-01266-9. PMID:33005001<ref>PMID:33005001</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6jjl" style="background-color:#fffaf0;"></div>

==See Also==
*[[Heat Shock Protein structures|Heat Shock Protein structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Cho H]]
[[Category: Choi Y]]
[[Category: Kim S]]
[[Category: Lee HH]]