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| - | ==MYCOBACTERIUM TUBERCULOSIS UVRA== | + | |
| - | <StructureSection load='3zqj' size='340' side='right' caption='[[3zqj]], [[Resolution|resolution]] 3.40Å' scene=''> | + | ==Mycobacterium tuberculosis UvrA== |
| | + | <StructureSection load='3zqj' size='340' side='right'caption='[[3zqj]], [[Resolution|resolution]] 3.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3zqj]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2ygr 2ygr]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZQJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZQJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3zqj]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2ygr 2ygr]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZQJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZQJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.4Å</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=3zqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zqj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zqj RCSB], [http://www.ebi.ac.uk/pdbsum/3zqj PDBsum]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=3zqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zqj OCA], [https://pdbe.org/3zqj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zqj RCSB], [https://www.ebi.ac.uk/pdbsum/3zqj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zqj ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UVRA_MYCTU UVRA_MYCTU]] The UvrABC repair system catalyzes the recognition and processing of DNA lesions. UvrA is an ATPase and a DNA-binding protein. A damage recognition complex composed of 2 UvrA and 2 UvrB subunits scans DNA for abnormalities. When the presence of a lesion has been verified by UvrB, the UvrA molecules dissociate. Alone it slightly inhibits RecA-mediated DNA strand exchange, in concert with UvrD1 greatly inhibits RecA-mediated DNA strand exchange.<ref>PMID:20455546</ref> <ref>PMID:22467787</ref> | + | [https://www.uniprot.org/uniprot/UVRA_MYCTU UVRA_MYCTU] The UvrABC repair system catalyzes the recognition and processing of DNA lesions. UvrA is an ATPase and a DNA-binding protein. A damage recognition complex composed of 2 UvrA and 2 UvrB subunits scans DNA for abnormalities. When the presence of a lesion has been verified by UvrB, the UvrA molecules dissociate. Alone it slightly inhibits RecA-mediated DNA strand exchange, in concert with UvrD1 greatly inhibits RecA-mediated DNA strand exchange.<ref>PMID:20455546</ref> <ref>PMID:22467787</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | 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 3zqj" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Mycobacterium tuberculosis]] | | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Bortoluzzi, A]] | + | [[Category: Bortoluzzi A]] |
| - | [[Category: Bottger, E C]] | + | [[Category: Bottger EC]] |
| - | [[Category: Davis, E O]] | + | [[Category: Davis EO]] |
| - | [[Category: Guthlein, C]] | + | [[Category: Guthlein C]] |
| - | [[Category: Houghton, J]] | + | [[Category: Houghton J]] |
| - | [[Category: Khanduja, J S]] | + | [[Category: Khanduja JS]] |
| - | [[Category: Muniyappa, K]] | + | [[Category: Muniyappa K]] |
| - | [[Category: Penco, A]] | + | [[Category: Penco A]] |
| - | [[Category: Relini, A]] | + | [[Category: Relini A]] |
| - | [[Category: Rizzi, M]] | + | [[Category: Rizzi M]] |
| - | [[Category: Rossi, F]] | + | [[Category: Rossi F]] |
| - | [[Category: Sander, P]] | + | [[Category: Sander P]] |
| - | [[Category: Springer, B]] | + | [[Category: Springer B]] |
| - | [[Category: Dna binding protein]]
| + | |
| - | [[Category: Nucleotide excision repair]]
| + | |
| Structural highlights
Function
UVRA_MYCTU The UvrABC repair system catalyzes the recognition and processing of DNA lesions. UvrA is an ATPase and a DNA-binding protein. A damage recognition complex composed of 2 UvrA and 2 UvrB subunits scans DNA for abnormalities. When the presence of a lesion has been verified by UvrB, the UvrA molecules dissociate. Alone it slightly inhibits RecA-mediated DNA strand exchange, in concert with UvrD1 greatly inhibits RecA-mediated DNA strand exchange.[1] [2]
Publication Abstract from PubMed
Mycobacterium tuberculosis is an extremely well adapted intracellular human pathogen that is exposed to multiple DNA damaging chemical assaults originating from the host defence mechanisms. As a consequence, this bacterium is thought to possess highly efficient DNA repair machineries, the nucleotide excision repair (NER) system amongst these. Although NER is of central importance to DNA repair in M. tuberculosis, our understanding of the processes in this species is limited. The conserved UvrABC endonuclease represents the multi-enzymatic core in bacterial NER, where the UvrA ATPase provides the DNA lesion-sensing function. The herein reported genetic analysis demonstrates that M. tuberculosis UvrA is important for the repair of nitrosative and oxidative DNA damage. Moreover, our biochemical and structural characterization of recombinant M. tuberculosis UvrA contributes new insights into its mechanism of action. In particular, the structural investigation reveals an unprecedented conformation of the UvrB-binding domain that we propose to be of functional relevance. Taken together, our data suggest UvrA as a potential target for the development of novel anti-tubercular agents and provide a biochemical framework for the identification of small-molecule inhibitors interfering with the NER activity in M. tuberculosis.
The biological and structural characterization of Mycobacterium tuberculosis UvrA provides novel insights into its mechanism of action.,Rossi F, Khanduja JS, Bortoluzzi A, Houghton J, Sander P, Guthlein C, Davis EO, Springer B, Bottger EC, Relini A, Penco A, Muniyappa K, Rizzi M Nucleic Acids Res. 2011 May 27. PMID:21622956[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Singh P, Patil KN, Khanduja JS, Kumar PS, Williams A, Rossi F, Rizzi M, Davis EO, Muniyappa K. Mycobacterium tuberculosis UvrD1 and UvrA proteins suppress DNA strand exchange promoted by cognate and noncognate RecA proteins. Biochemistry. 2010 Jun 15;49(23):4872-83. doi: 10.1021/bi902021d. PMID:20455546 doi:http://dx.doi.org/10.1021/bi902021d
- ↑ Houghton J, Townsend C, Williams AR, Rodgers A, Rand L, Walker KB, Bottger EC, Springer B, Davis EO. Important role for Mycobacterium tuberculosis UvrD1 in pathogenesis and persistence apart from its function in nucleotide excision repair. J Bacteriol. 2012 Jun;194(11):2916-23. doi: 10.1128/JB.06654-11. Epub 2012 Mar, 30. PMID:22467787 doi:http://dx.doi.org/10.1128/JB.06654-11
- ↑ Rossi F, Khanduja JS, Bortoluzzi A, Houghton J, Sander P, Guthlein C, Davis EO, Springer B, Bottger EC, Relini A, Penco A, Muniyappa K, Rizzi M. The biological and structural characterization of Mycobacterium tuberculosis UvrA provides novel insights into its mechanism of action. Nucleic Acids Res. 2011 May 27. PMID:21622956 doi:10.1093/nar/gkr271
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