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| | <StructureSection load='6a7v' size='340' side='right'caption='[[6a7v]], [[Resolution|resolution]] 1.67Å' scene=''> | | <StructureSection load='6a7v' size='340' side='right'caption='[[6a7v]], [[Resolution|resolution]] 1.67Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6a7v]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6A7V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6A7V FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6a7v]] is a 8 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=6A7V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6A7V FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.67Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">vapC11, Rv1561, MTCY48.04c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU]), vapB11, Rv1560, MTCY48.05c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=6a7v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a7v OCA], [http://pdbe.org/6a7v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6a7v RCSB], [http://www.ebi.ac.uk/pdbsum/6a7v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6a7v 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=6a7v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a7v OCA], [https://pdbe.org/6a7v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6a7v RCSB], [https://www.ebi.ac.uk/pdbsum/6a7v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6a7v ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/VPC11_MYCTU VPC11_MYCTU]] Toxic component of a type II toxin-antitoxin (TA) system. Acts as an RNase. Upon expression in E.coli and M.smegmatis inhibits translation, cell growth and colony formation. Its toxic effects on cell growth and colony formation are neutralized by coexpression with cognate antitoxin VapB11; the effect on translation has not been tested but is probably also neutralized.<ref>PMID:19016878</ref> <ref>PMID:20011113</ref> [[http://www.uniprot.org/uniprot/VPB11_MYCTU VPB11_MYCTU]] Antitoxin component of a type II toxin-antitoxin (TA) system. Upon expression in E.coli and M.smegmatis neutralizes the effect of cognate toxin VapC11.<ref>PMID:19016878</ref> <ref>PMID:20011113</ref> <ref>PMID:15718296</ref> | + | [https://www.uniprot.org/uniprot/VPC11_MYCTU VPC11_MYCTU] Toxic component of a type II toxin-antitoxin (TA) system. Acts as an RNase. Upon expression in E.coli and M.smegmatis inhibits translation, cell growth and colony formation. Its toxic effects on cell growth and colony formation are neutralized by coexpression with cognate antitoxin VapB11; the effect on translation has not been tested but is probably also neutralized.<ref>PMID:19016878</ref> <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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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Ribonuclease|Ribonuclease]] | + | *[[Ribonuclease 3D structures|Ribonuclease 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Myctu]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Deep, A]] | + | [[Category: Deep A]] |
| - | [[Category: Thakur, K G]] | + | [[Category: Thakur KG]] |
| - | [[Category: Endoribonuclease]]
| + | |
| - | [[Category: Rv1560-rv1561]]
| + | |
| - | [[Category: Toxin]]
| + | |
| - | [[Category: Toxin-antitoxin complex]]
| + | |
| - | [[Category: Trnase]]
| + | |
| - | [[Category: Vapbc]]
| + | |
| Structural highlights
Function
VPC11_MYCTU Toxic component of a type II toxin-antitoxin (TA) system. Acts as an RNase. Upon expression in E.coli and M.smegmatis inhibits translation, cell growth and colony formation. Its toxic effects on cell growth and colony formation are neutralized by coexpression with cognate antitoxin VapB11; the effect on translation has not been tested but is probably also neutralized.[1] [2]
Publication Abstract from PubMed
Toxin-antitoxin (TA) systems are involved in diverse physiological processes in prokaryotes, but their exact role in Mycobacterium tuberculosis (Mtb) virulence and in vivo stress adaptation has not been extensively studied. Here, we demonstrate that the VapBC11 TA module is essential for Mtb to establish infection in guinea pigs. RNA-sequencing revealed that overexpression of VapC11 toxin results in metabolic slowdown, suggesting that modulation of the growth rate is an essential strategy for in vivo survival. Interestingly, overexpression of VapC11 resulted in the upregulation of chromosomal TA genes, suggesting the existence of highly coordinated crosstalk among TA systems. In this study, we also present the crystal structure of the VapBC11 heterooctameric complex at 1.67 A resolution. Binding kinetic studies suggest that the binding affinities of toxin-substrate and toxin-antitoxin interactions are comparable. We used a combination of structural studies, molecular docking, mutational analysis and in vitro ribonuclease assays to enhance our understanding of the mode of substrate recognition by the VapC11 toxin. Furthermore, we have also designed peptide-based inhibitors to target VapC11 ribonuclease activity. Taken together, we propose that the structure-guided design of inhibitors against in vivo essential ribonucleases might be a novel strategy to hasten clearance of intracellular Mtb.
Structural, functional and biological insights into the role of Mycobacterium tuberculosis VapBC11 toxin-antitoxin system: targeting a tRNase to tackle mycobacterial adaptation.,Deep A, Tiwari P, Agarwal S, Kaundal S, Kidwai S, Singh R, Thakur KG Nucleic Acids Res. 2018 Nov 30;46(21):11639-11655. doi: 10.1093/nar/gky924. PMID:30329074[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gupta A. Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. FEMS Microbiol Lett. 2009 Jan;290(1):45-53. doi:, 10.1111/j.1574-6968.2008.01400.x. Epub 2008 Nov 10. PMID:19016878 doi:http://dx.doi.org/10.1111/j.1574-6968.2008.01400.x
- ↑ 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
- ↑ Deep A, Tiwari P, Agarwal S, Kaundal S, Kidwai S, Singh R, Thakur KG. Structural, functional and biological insights into the role of Mycobacterium tuberculosis VapBC11 toxin-antitoxin system: targeting a tRNase to tackle mycobacterial adaptation. Nucleic Acids Res. 2018 Nov 30;46(21):11639-11655. doi: 10.1093/nar/gky924. PMID:30329074 doi:http://dx.doi.org/10.1093/nar/gky924
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