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| | <StructureSection load='6ox6' size='340' side='right'caption='[[6ox6]], [[Resolution|resolution]] 2.17Å' scene=''> | | <StructureSection load='6ox6' size='340' side='right'caption='[[6ox6]], [[Resolution|resolution]] 2.17Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ox6]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_aeruginosus"_(schroeter_1872)_trevisan_1885 "bacillus aeruginosus" (schroeter 1872) trevisan 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OX6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OX6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ox6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OX6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OX6 FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.17Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CGU42_21755, IPC3_19385 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=287 "Bacillus aeruginosus" (Schroeter 1872) Trevisan 1885]), CGU42_21760, EGJ96_33750, EQH76_16385, IPC3_19390, PA34_000540 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=287 "Bacillus aeruginosus" (Schroeter 1872) Trevisan 1885])</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=6ox6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ox6 OCA], [https://pdbe.org/6ox6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ox6 RCSB], [https://www.ebi.ac.uk/pdbsum/6ox6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ox6 ProSAT]</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=6ox6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ox6 OCA], [http://pdbe.org/6ox6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ox6 RCSB], [http://www.ebi.ac.uk/pdbsum/6ox6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ox6 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/TSE6_PSEAE TSE6_PSEAE] Type VI secretion exported toxin that acts as a glycohydrolase on bacterial target cells and degrades the essential dinucleotides NAD(+) and NADP(+), thereby inducing bacteriostasis. The activity resides in the C-terminal region that is initially neutralized by the cognate immunity protein Tsi6.<ref>PMID:26456113</ref> <ref>PMID:30177742</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ahmad, S]] | |
| - | [[Category: Structural genomic]] | |
| - | [[Category: Joachimiak, A]] | |
| - | [[Category: Satchell, K J.F]] | |
| - | [[Category: Savchenko, A]] | |
| - | [[Category: Skarina, T]] | |
| - | [[Category: Stogios, P J]] | |
| - | [[Category: Whitney, J]] | |
| - | [[Category: Alarmone]] | |
| - | [[Category: Bacterial warfare]] | |
| - | [[Category: Csgid]] | |
| | [[Category: Pseudomonas aeruginosa]] | | [[Category: Pseudomonas aeruginosa]] |
| - | [[Category: Transferase]] | + | [[Category: Ahmad S]] |
| - | [[Category: Type vi secretion]] | + | [[Category: Joachimiak A]] |
| | + | [[Category: Satchell KJF]] |
| | + | [[Category: Savchenko A]] |
| | + | [[Category: Skarina T]] |
| | + | [[Category: Stogios PJ]] |
| | + | [[Category: Whitney J]] |
| Structural highlights
Function
TSE6_PSEAE Type VI secretion exported toxin that acts as a glycohydrolase on bacterial target cells and degrades the essential dinucleotides NAD(+) and NADP(+), thereby inducing bacteriostasis. The activity resides in the C-terminal region that is initially neutralized by the cognate immunity protein Tsi6.[1] [2]
Publication Abstract from PubMed
Bacteria have evolved sophisticated mechanisms to inhibit the growth of competitors(1). One such mechanism involves type VI secretion systems, which bacteria can use to inject antibacterial toxins directly into neighbouring cells. Many of these toxins target the integrity of the cell envelope, but the full range of growth inhibitory mechanisms remains unknown(2). Here we identify a type VI secretion effector, Tas1, in the opportunistic pathogen Pseudomonas aeruginosa. The crystal structure of Tas1 shows that it is similar to enzymes that synthesize (p)ppGpp, a broadly conserved signalling molecule in bacteria that modulates cell growth rate, particularly in response to nutritional stress(3). However, Tas1 does not synthesize (p)ppGpp; instead, it pyrophosphorylates adenosine nucleotides to produce (p)ppApp at rates of nearly 180,000 molecules per minute. Consequently, the delivery of Tas1 into competitor cells drives rapid accumulation of (p)ppApp, depletion of ATP, and widespread dysregulation of essential metabolic pathways, thereby resulting in target cell death. Our findings reveal a previously undescribed mechanism for interbacterial antagonism and demonstrate a physiological role for the metabolite (p)ppApp in bacteria.
An interbacterial toxin inhibits target cell growth by synthesizing (p)ppApp.,Ahmad S, Wang B, Walker MD, Tran HR, Stogios PJ, Savchenko A, Grant RA, McArthur AG, Laub MT, Whitney JC Nature. 2019 Nov 6. pii: 10.1038/s41586-019-1735-9. doi:, 10.1038/s41586-019-1735-9. PMID:31695193[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Whitney JC, Quentin D, Sawai S, LeRoux M, Harding BN, Ledvina HE, Tran BQ, Robinson H, Goo YA, Goodlett DR, Raunser S, Mougous JD. An interbacterial NAD(P)(+) glycohydrolase toxin requires elongation factor Tu for delivery to target cells. Cell. 2015 Oct 22;163(3):607-19. doi: 10.1016/j.cell.2015.09.027. Epub 2015 Oct, 8. PMID:26456113 doi:http://dx.doi.org/10.1016/j.cell.2015.09.027
- ↑ Quentin D, Ahmad S, Shanthamoorthy P, Mougous JD, Whitney JC, Raunser S. Mechanism of loading and translocation of type VI secretion system effector Tse6. Nat Microbiol. 2018 Sep 3. pii: 10.1038/s41564-018-0238-z. doi:, 10.1038/s41564-018-0238-z. PMID:30177742 doi:http://dx.doi.org/10.1038/s41564-018-0238-z
- ↑ Ahmad S, Wang B, Walker MD, Tran HR, Stogios PJ, Savchenko A, Grant RA, McArthur AG, Laub MT, Whitney JC. An interbacterial toxin inhibits target cell growth by synthesizing (p)ppApp. Nature. 2019 Nov 6. pii: 10.1038/s41586-019-1735-9. doi:, 10.1038/s41586-019-1735-9. PMID:31695193 doi:http://dx.doi.org/10.1038/s41586-019-1735-9
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