View source for 6ucr


==Structure of ClpC1-NTD L92S L96P==
<StructureSection load='6ucr' size='340' side='right'caption='[[6ucr]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ucr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UCR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UCR 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]] 2.3&#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></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=6ucr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ucr OCA], [https://pdbe.org/6ucr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ucr RCSB], [https://www.ebi.ac.uk/pdbsum/6ucr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ucr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CLPC1_MYCTU CLPC1_MYCTU] ATP-dependent specificity component of the Clp protease. It directs the protease to specific substrates. Can perform chaperone functions in the absence of ClpP (By similarity). Degrades anti-sigma-E factor RseA in the presence of ClpP2.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The biological processes related to protein homeostasis in Mycobacterium tuberculosis, the etiologic agent of tuberculosis, have recently been established as critical pathways for therapeutic intervention. Proteins of particular interest are ClpC1 and the ClpC1-ClpP1-ClpP2 proteasome complex. The structure of the potent antituberculosis macrocyclic depsipeptide ecumicin complexed with the N-terminal domain of ClpC1 (ClpC1-NTD) is presented here. Crystals of the ClpC1-NTD-ecumicin complex were monoclinic (unit-cell parameters a = 80.0, b = 130.0, c = 112.0 A, beta = 90.07 degrees ; space group P21; 12 complexes per asymmetric unit) and diffracted to 2.5 A resolution. The structure was solved by molecular replacement using the self-rotation function to resolve space-group ambiguities. The new structure of the ecumicin complex showed a unique 1:2 (target:ligand) stoichiometry exploiting the intramolecular dyad in the alpha-helical fold of the target N-terminal domain. The structure of the ecumicin complex unveiled extensive interactions in the uniquely extended N-terminus, a critical binding site for the known cyclopeptide complexes. This structure, in comparison with the previously reported rufomycin I complex, revealed unique features that could be relevant for understanding the mechanism of action of these potential antituberculosis drug leads. Comparison of the ecumicin complex and the ClpC1-NTD-L92S/L96P double-mutant structure with the available structures of rufomycin I and cyclomarin A complexes revealed a range of conformational changes available to this small N-terminal helical domain and the minor helical alterations involved in the antibiotic-resistance mechanism. The different modes of binding and structural alterations could be related to distinct modes of action.

Structure of the N-terminal domain of ClpC1 in complex with the antituberculosis natural product ecumicin reveals unique binding interactions.,Wolf NM, Lee H, Zagal D, Nam JW, Oh DC, Lee H, Suh JW, Pauli GF, Cho S, Abad-Zapatero C Acta Crystallogr D Struct Biol. 2020 May 1;76(Pt 5):458-471. doi:, 10.1107/S2059798320004027. Epub 2020 Apr 23. PMID:32355042<ref>PMID:32355042</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6ucr" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Abad-Zapatero C]]
[[Category: Wolf NM]]