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| | ==Toxin VapC21 from Mycobacterium tuberculosis== | | ==Toxin VapC21 from Mycobacterium tuberculosis== |
| - | <StructureSection load='5sv2' size='340' side='right' caption='[[5sv2]], [[Resolution|resolution]] 1.31Å' scene=''> | + | <StructureSection load='5sv2' size='340' side='right'caption='[[5sv2]], [[Resolution|resolution]] 1.31Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5sv2]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SV2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5SV2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5sv2]] 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=5SV2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SV2 FirstGlance]. <br> |
| - | </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=5sv2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sv2 OCA], [http://pdbe.org/5sv2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5sv2 RCSB], [http://www.ebi.ac.uk/pdbsum/5sv2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5sv2 ProSAT]</span></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]] 1.31Å</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=5sv2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sv2 OCA], [https://pdbe.org/5sv2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5sv2 RCSB], [https://www.ebi.ac.uk/pdbsum/5sv2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5sv2 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/VPC21_MYCTU VPC21_MYCTU]] Toxic component of a type II toxin-antitoxin (TA) module. An RNase (By similarity). Upon expression in M.smegmatis inhibits colony formation. Its toxic effect is neutralized by coexpression with cognate antitoxin VapB21.[HAMAP-Rule:MF_00265]<ref>PMID:20011113</ref> | + | [https://www.uniprot.org/uniprot/VPC21_MYCTU VPC21_MYCTU] Toxic component of a type II toxin-antitoxin (TA) module. An RNase (By similarity). Upon expression in M.smegmatis inhibits colony formation. Its toxic effect is neutralized by coexpression with cognate antitoxin VapB21.[HAMAP-Rule:MF_00265]<ref>PMID:20011113</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5sv2" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5sv2" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Ribonuclease 3D structures|Ribonuclease 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Valadares, N F]] | + | [[Category: Large Structures]] |
| - | [[Category: Hydrolase]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Rnase]] | + | [[Category: Valadares NF]] |
| - | [[Category: Toxin-antitoxin]]
| + | |
| - | [[Category: Vapbc]]
| + | |
| - | [[Category: Vapc]]
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| - | [[Category: Vapc21]]
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| Structural highlights
Function
VPC21_MYCTU Toxic component of a type II toxin-antitoxin (TA) module. An RNase (By similarity). Upon expression in M.smegmatis inhibits colony formation. Its toxic effect is neutralized by coexpression with cognate antitoxin VapB21.[HAMAP-Rule:MF_00265][1]
Publication Abstract from PubMed
Persisters are individual bacterial cells that exhibit a phenotype characterized by slow growth, low metabolic rate and multidrug tolerance. The processes that drive cells into a persistence state constitute an active but incipient research field, and structural data regarding its components are scarce. The molecular targets of many therapeutic drugs are involved in cell wall synthesis and cell division, and these cellular processes are down-regulated in persister cells, consequently these cells are more likely to survive antibiotic treatment. Toxin-antitoxin systems were shown to have a leading role in the formation of persisters, and several pathogenic bacteria display a wide array of these systems. The Mycobacterium tuberculosis H37Rv genome presents 88 toxin-antitoxin loci, of which 47 code for members of the VapBC protein family. To date, only four crystal structures of Mycobacterium tuberculosis VapBC complexes are available, and all of them present the toxin bound to and inhibited by the antitoxin. We present the 1.31 A resolution structure of VapC21, the first structure of a Mycobacterium tuberculosis VapC toxin in the absence of its cognate inhibitory antitoxin. Our data show that VapC21 is a dimer in solution, with conserved active site architecture and an extensive antitoxin binding groove. Additionally, the strategy used to mutate a putative catalytic residue allowing the expression and purification of soluble VapC21 will pave the way for the resolution of more toxin structures in the absence of antitoxins. Taken together, our findings represent an important step in unraveling the molecular mechanisms related to persistence, which will contribute for the design of faster and more efficient therapeutic approaches for the treatment of tuberculosis, particularly for infections with multidrug-resistant strains.
Crystal structure of VapC21 from Mycobacterium tuberculosis at 1.31 A resolution.,Jardim P, Santos IC, Barbosa JA, de Freitas SM, Valadares NF Biochem Biophys Res Commun. 2016 Sep 23;478(3):1370-5. doi:, 10.1016/j.bbrc.2016.08.130. Epub 2016 Aug 27. PMID:27576202[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ramage HR, Connolly LE, Cox JS. Comprehensive functional analysis of Mycobacterium tuberculosis toxin-antitoxin systems: implications for pathogenesis, stress responses, and evolution. PLoS Genet. 2009 Dec;5(12):e1000767. doi: 10.1371/journal.pgen.1000767. Epub 2009, Dec 11. PMID:20011113 doi:http://dx.doi.org/10.1371/journal.pgen.1000767
- ↑ Jardim P, Santos IC, Barbosa JA, de Freitas SM, Valadares NF. Crystal structure of VapC21 from Mycobacterium tuberculosis at 1.31 A resolution. Biochem Biophys Res Commun. 2016 Sep 23;478(3):1370-5. doi:, 10.1016/j.bbrc.2016.08.130. Epub 2016 Aug 27. PMID:27576202 doi:http://dx.doi.org/10.1016/j.bbrc.2016.08.130
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