3wdc
From Proteopedia
(Difference between revisions)
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| - | + | ==N-terminal domain of Mycobacterium tuberculosis ClpC1 bound to Cyclomarin A== | |
| - | + | <StructureSection load='3wdc' size='340' side='right' caption='[[3wdc]], [[Resolution|resolution]] 1.18Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[3wdc]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884] and [http://en.wikipedia.org/wiki/Chainia_sp. Chainia sp.]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WDC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WDC FirstGlance]. <br> | |
| - | ==Function== | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr> |
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MLE:N-METHYLLEUCINE'>MLE</scene>, <scene name='pdbligand=WLU:(4R)-5-HYDROXY-N-METHYL-L-LEUCINE'>WLU</scene>, <scene name='pdbligand=WPA:(BETAR)-BETA-METHOXY-L-PHENYLALANINE'>WPA</scene>, <scene name='pdbligand=WRP:(BETAR)-BETA-HYDROXY-1-[(3R)-3-HYDROXY-2-METHYLBUTAN-2-YL]-L-TRYPTOPHAN'>WRP</scene>, <scene name='pdbligand=WVL:(2S,3R)-2-AMINO-3,5-DIMETHYLHEX-4-ENOIC+ACID'>WVL</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3wdb|3wdb]], [[3wdd|3wdd]], [[3wde|3wde]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">clpC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3wdc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wdc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3wdc RCSB], [http://www.ebi.ac.uk/pdbsum/3wdc PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
[[http://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. | [[http://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 == | ||
| + | Cyclomarin A (CymA) was identified as a mycobactericidal compound targeting ClpC1. However, the target was identified based on pulldown experiments and in vitro binding data, without direct functional evidence in mycobacteria. Here we show that CymA specifically binds to the N-terminal domain of ClpC1. In addition we have determined the co-crystal structure of CymA bound to the N-terminal domain of ClpC1 to high resolution. Based on the structure of the complex several mutations were engineered into ClpC1, which showed reduced CymA binding in vitro. The ClpC1 mutants were overexpressed in mycobacteria and two showed resistance to CymA, providing the first direct evidence that ClpC1 is the target of CymA. Phe(80) is important in vitro and in cells for the ClpC1-CymA interaction and this explains why other bacteria are resistant to CymA. A model for how CymA binding to the N-terminal domain of ClpC1 leads to uncontrolled proteolysis by the associated ClpP protease machinery is discussed. | ||
| - | + | Structural basis of mycobacterial inhibition by cyclomarin A.,Vasudevan D, Rao SP, Noble CG J Biol Chem. 2013 Oct 25;288(43):30883-91. doi: 10.1074/jbc.M113.493767. Epub, 2013 Sep 10. PMID:24022489<ref>PMID:24022489</ref> | |
| - | + | ||
| - | == | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| - | [[Category: Chainia sp | + | == References == |
| - | [[Category: Noble, C G | + | <references/> |
| - | [[Category: Vasudevan, D | + | __TOC__ |
| + | </StructureSection> | ||
| + | [[Category: Chainia sp]] | ||
| + | [[Category: Noble, C G]] | ||
| + | [[Category: Vasudevan, D]] | ||
[[Category: Chaperone]] | [[Category: Chaperone]] | ||
[[Category: Chaperone-antimicrobial protein complex]] | [[Category: Chaperone-antimicrobial protein complex]] | ||
Revision as of 06:38, 25 December 2014
N-terminal domain of Mycobacterium tuberculosis ClpC1 bound to Cyclomarin A
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