3wde

From Proteopedia

(Difference between revisions)

Revision as of 18:18, 4 August 2016

Mutant N-terminal domain of Mycobacterium tuberculosis ClpC1, F80Y, bound to Cyclomarin A

Structural highlights

3wde is a 2 chain structure with sequence from "bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884 and Chainia sp.. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:	, , , ,
Related:	3wdb, 3wdc, 3wdd
Gene:	clpC ("Bacillus tuberculosis" (Zopf 1883) Klein 1884)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Vasudevan D, Rao SP, Noble CG. Structural basis of mycobacterial inhibition by cyclomarin A. J Biol Chem. 2013 Oct 25;288(43):30883-91. doi: 10.1074/jbc.M113.493767. Epub, 2013 Sep 10. PMID:24022489 doi:http://dx.doi.org/10.1074/jbc.M113.493767

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3wde"

Categories: Chainia sp | Noble, C G | Vasudevan, D | Chaperone | Chaperone-antimicrobial protein complex

@@ Line 1: / Line 1: @@
 ==Mutant N-terminal domain of Mycobacterium tuberculosis ClpC1, F80Y, bound to Cyclomarin A==
 <StructureSection load='3wde' size='340' side='right' caption='[[3wde]], [[Resolution|resolution]] 1.44&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3wdb|3wdb]], [[3wdc|3wdc]], [[3wdd|3wdd]]</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=3wde FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wde OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3wde RCSB], [http://www.ebi.ac.uk/pdbsum/3wde PDBsum]</span></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=3wde FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wde OCA], [http://pdbe.org/3wde PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3wde RCSB], [http://www.ebi.ac.uk/pdbsum/3wde PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3wde ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3wde" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

3wde

From Proteopedia

Revision as of 18:18, 4 August 2016

Mutant N-terminal domain of Mycobacterium tuberculosis ClpC1, F80Y, bound to Cyclomarin A

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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