8a8u
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8a8u]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8A8U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A8U FirstGlance]. <br> | <table><tr><td colspan='2'>[[8a8u]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8A8U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A8U FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.62Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</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=8a8u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a8u OCA], [https://pdbe.org/8a8u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a8u RCSB], [https://www.ebi.ac.uk/pdbsum/8a8u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a8u 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=8a8u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a8u OCA], [https://pdbe.org/8a8u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a8u RCSB], [https://www.ebi.ac.uk/pdbsum/8a8u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a8u ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| - | The unfoldase ClpC1 is one of the most exciting drug targets against tuberculosis. This AAA+ unfoldase works in cooperation with the ClpP1P2 protease and is the target of at least four natural product antibiotics: cyclomarin, ecumicin, lassomycin and rufomycin. Although these molecules are promising starting points for drug development, their mechanisms of action remain largely unknown. Taking advantage of a middle domain mutant, we determined the first structure of Mycobacterium tuberculosis ClpC1 in its apo, cyclomarin and ecumicin bound states via cryo- | + | The unfoldase ClpC1 is one of the most exciting drug targets against tuberculosis. This AAA+ unfoldase works in cooperation with the ClpP1P2 protease and is the target of at least four natural product antibiotics: cyclomarin, ecumicin, lassomycin, and rufomycin. Although these molecules are promising starting points for drug development, their mechanisms of action remain largely unknown. Taking advantage of a middle domain mutant, we determined the first structure of Mycobacterium tuberculosis ClpC1 in its apo, cyclomarin-, and ecumicin-bound states via cryo-EM. The obtained structure displays features observed in other members of the AAA+ family and provides a map for further drug development. While the apo and cyclomarin-bound structures are indistinguishable and have N-terminal domains that are invisible in their respective EM maps, around half of the ecumicin-bound ClpC1 particles display three of their six N-terminal domains in an extended conformation. Our structural observations suggest a mechanism where ecumicin functions by mimicking substrate binding, leading to ATPase activation and changes in protein degradation profile. |
| - | Structure of the drug target ClpC1 unfoldase in action provides insights on antibiotic mechanism of action.,Weinhaupl K, Gragera M, Bueno-Carrasco MT, Arranz R, Krandor O, Akopian T, Soares R, Rubin E, Felix J, Fraga H J Biol Chem. 2022 | + | Structure of the drug target ClpC1 unfoldase in action provides insights on antibiotic mechanism of action.,Weinhaupl K, Gragera M, Bueno-Carrasco MT, Arranz R, Krandor O, Akopian T, Soares R, Rubin E, Felix J, Fraga H J Biol Chem. 2022 Nov;298(11):102553. doi: 10.1016/j.jbc.2022.102553. Epub 2022 , Oct 6. PMID:36208775<ref>PMID:36208775</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 8a8u" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 8a8u" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Clp protease 3D structures|Clp protease 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Mycobacterium tuberculosis ClpC1 hexamer structure
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