View source for 6hwn


==Structure of Thermus thermophilus ClpP in complex with a tripeptide.==
<StructureSection load='6hwn' size='340' side='right'caption='[[6hwn]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6hwn]] is a 14 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HWN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HWN 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]] 1.95&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=6hwn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hwn OCA], [https://pdbe.org/6hwn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hwn RCSB], [https://www.ebi.ac.uk/pdbsum/6hwn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hwn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CLPP_THET8 CLPP_THET8] 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.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Coordinated conformational transitions in oligomeric enzymatic complexes modulate function in response to substrates and play a crucial role in enzyme inhibition and activation. Caseinolytic protease (ClpP) is a tetradecameric complex, which has emerged as a drug target against multiple pathogenic bacteria. Activation of different ClpPs by inhibitors has been independently reported from drug development efforts, but no rationale for inhibitor-induced activation has been hitherto proposed. Using an integrated approach that includes x-ray crystallography, solid- and solution-state nuclear magnetic resonance, molecular dynamics simulations, and isothermal titration calorimetry, we show that the proteasome inhibitor bortezomib binds to the ClpP active-site serine, mimicking a peptide substrate, and induces a concerted allosteric activation of the complex. The bortezomib-activated conformation also exhibits a higher affinity for its cognate unfoldase ClpX. We propose a universal allosteric mechanism, where substrate binding to a single subunit locks ClpP into an active conformation optimized for chaperone association and protein processive degradation.

Mechanism of the allosteric activation of the ClpP protease machinery by substrates and active-site inhibitors.,Felix J, Weinhaupl K, Chipot C, Dehez F, Hessel A, Gauto DF, Morlot C, Abian O, Gutsche I, Velazquez-Campoy A, Schanda P, Fraga H Sci Adv. 2019 Sep 4;5(9):eaaw3818. doi: 10.1126/sciadv.aaw3818. eCollection 2019 , Sep. PMID:31517045<ref>PMID:31517045</ref>

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

==See Also==
*[[Clp protease 3D structures|Clp protease 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Thermus thermophilus]]
[[Category: Felix J]]
[[Category: Fraga H]]
[[Category: Morlot C]]
[[Category: Schanda P]]