7mk5: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7mk5]] is a 28 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=7MK5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MK5 FirstGlance]. <br>
<table><tr><td colspan='2'>[[7mk5]] is a 28 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=7MK5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MK5 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=ZGV:4-[(1E)-3-{[(2E,4E,6E,8S)-8-hydroxy-4-methyldeca-2,4,6-trienoyl]amino}-3-oxoprop-1-en-1-yl]azete-1(2H)-carboxylic+acid'>ZGV</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.95&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=ZGV:4-[(1E)-3-{[(2E,4E,6E,8S)-8-hydroxy-4-methyldeca-2,4,6-trienoyl]amino}-3-oxoprop-1-en-1-yl]azete-1(2H)-carboxylic+acid'>ZGV</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=7mk5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mk5 OCA], [https://pdbe.org/7mk5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mk5 RCSB], [https://www.ebi.ac.uk/pdbsum/7mk5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mk5 ProSAT]</span></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=7mk5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mk5 OCA], [https://pdbe.org/7mk5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mk5 RCSB], [https://www.ebi.ac.uk/pdbsum/7mk5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mk5 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/CLPP_ECOLI CLPP_ECOLI] Cleaves peptides in various proteins in a process that requires ATP hydrolysis. Has a chymotrypsin-like activity. Plays a major role in the degradation of misfolded proteins. May play the role of a master protease which is attracted to different substrates by different specificity factors such as ClpA or ClpX.
[https://www.uniprot.org/uniprot/CLPP_ECOLI CLPP_ECOLI] Cleaves peptides in various proteins in a process that requires ATP hydrolysis. Has a chymotrypsin-like activity. Plays a major role in the degradation of misfolded proteins. May play the role of a master protease which is attracted to different substrates by different specificity factors such as ClpA or ClpX.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The caseinolytic protease (ClpP) is part of a highly conserved proteolytic complex whose disruption can lead to antibacterial activity but for which few specific inhibitors have been discovered. Specialized metabolites produced by bacteria have been shaped by evolution for specific functions, making them a potential source of selective ClpP inhibitors. Here, we describe a target-directed genome mining strategy for discovering ClpP-interacting compounds by searching for biosynthetic gene clusters that contain duplicated copies of ClpP as putative antibiotic resistance genes. We identify a widespread family of ClpP-associated clusters that are known to produce pyrrolizidine alkaloids but whose connection to ClpP has never been made. We show that previously characterized molecules do not affect ClpP function but are shunt metabolites derived from the genuine product of these gene clusters, a reactive covalent ClpP inhibitor. Focusing on one such cryptic gene cluster from Streptomyces cattleya, we identify the relevant inhibitor, which we name clipibicyclene, and show that it potently and selectively inactivates ClpP. Finally, we solve the crystal structure of clipibicyclene-modified Escherichia coli ClpP. Clipibicyclene's discovery reveals the authentic function of a family of natural products whose specificity for ClpP and abundance in nature illuminate the role of eco-evolutionary forces during bacterial competition.


ClpP inhibitors are produced by a widespread family of bacterial gene clusters.,Culp EJ, Sychantha D, Hobson C, Pawlowski AC, Prehna G, Wright GD Nat Microbiol. 2022 Mar;7(3):451-462. doi: 10.1038/s41564-022-01073-4. Epub 2022 , Mar 4. PMID:35246663<ref>PMID:35246663</ref>
==See Also==
 
*[[Clp protease 3D structures|Clp protease 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
*[[Heat Shock Protein structures|Heat Shock Protein structures]]
</div>
<div class="pdbe-citations 7mk5" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>

Revision as of 10:19, 3 April 2024

Crystal structure of Escherichia coli ClpP covalently inhibited by clipibicycleneCrystal structure of Escherichia coli ClpP covalently inhibited by clipibicyclene

Structural highlights

7mk5 is a 28 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.95Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CLPP_ECOLI Cleaves peptides in various proteins in a process that requires ATP hydrolysis. Has a chymotrypsin-like activity. Plays a major role in the degradation of misfolded proteins. May play the role of a master protease which is attracted to different substrates by different specificity factors such as ClpA or ClpX.

See Also

7mk5, resolution 2.95Å

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