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| | <StructureSection load='4qlp' size='340' side='right'caption='[[4qlp]], [[Resolution|resolution]] 1.10Å' scene=''> | | <StructureSection load='4qlp' size='340' side='right'caption='[[4qlp]], [[Resolution|resolution]] 1.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4qlp]] is a 2 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=4QLP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QLP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4qlp]] is a 2 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=4QLP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QLP FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HKBT1_4117, Rv3902c, Rv3903c, RVBD_3902c, RVBD_3903c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU]), HKBT1_4118, Rv3902c, Rv3903c, RVBD_3902c, RVBD_3903c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</td></tr> | + | </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=4qlp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qlp OCA], [https://pdbe.org/4qlp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qlp RCSB], [https://www.ebi.ac.uk/pdbsum/4qlp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qlp 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=4qlp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qlp OCA], [http://pdbe.org/4qlp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qlp RCSB], [http://www.ebi.ac.uk/pdbsum/4qlp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qlp ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/IFTNT_MYCTU IFTNT_MYCTU] Antitoxin for tuberculosis necrotizing toxin (TNT). Acts by binding directly to TNT, which inhibits NAD(+) glycohydrolase activity of TNT and protects M.tuberculosis from self-poisoning.<ref>PMID:26237511</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: Myctu]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Cingolani, G]] | + | [[Category: Cingolani G]] |
| - | [[Category: Doornbos, K S]] | + | [[Category: Doornbos KS]] |
| - | [[Category: Lokareddy, R K]] | + | [[Category: Lokareddy RK]] |
| - | [[Category: Niederweis, M]] | + | [[Category: Niederweis M]] |
| - | [[Category: Siroy, A]] | + | [[Category: Siroy A]] |
| - | [[Category: Speer, A]] | + | [[Category: Speer A]] |
| - | [[Category: Sun, J]] | + | [[Category: Sun J]] |
| - | [[Category: B-nad+ glycohydrolase]]
| + | |
| - | [[Category: Duf4237]]
| + | |
| - | [[Category: Factor rv3902c renamed here as immunity factor of tnt]]
| + | |
| - | [[Category: Hydrolase-protein binding complex]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Nad-binding domain]]
| + | |
| Structural highlights
Function
IFTNT_MYCTU Antitoxin for tuberculosis necrotizing toxin (TNT). Acts by binding directly to TNT, which inhibits NAD(+) glycohydrolase activity of TNT and protects M.tuberculosis from self-poisoning.[1]
Publication Abstract from PubMed
Mycobacterium tuberculosis (Mtb) induces necrosis of infected cells to evade immune responses. Recently, we found that Mtb uses the protein CpnT to kill human macrophages by secreting its C-terminal domain, named tuberculosis necrotizing toxin (TNT), which induces necrosis by an unknown mechanism. Here we show that TNT gains access to the cytosol of Mtb-infected macrophages, where it hydrolyzes the essential coenzyme NAD(+). Expression or injection of a noncatalytic TNT mutant showed no cytotoxicity in macrophages or in zebrafish zygotes, respectively, thus demonstrating that the NAD(+) glycohydrolase activity is required for TNT-induced cell death. To prevent self-poisoning, Mtb produces an immunity factor for TNT (IFT) that binds TNT and inhibits its activity. The crystal structure of the TNT-IFT complex revealed a new NAD(+) glycohydrolase fold of TNT, the founding member of a toxin family widespread in pathogenic microorganisms.
The tuberculosis necrotizing toxin kills macrophages by hydrolyzing NAD.,Sun J, Siroy A, Lokareddy RK, Speer A, Doornbos KS, Cingolani G, Niederweis M Nat Struct Mol Biol. 2015 Sep;22(9):672-8. doi: 10.1038/nsmb.3064. Epub 2015 Aug , 3. PMID:26237511[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sun J, Siroy A, Lokareddy RK, Speer A, Doornbos KS, Cingolani G, Niederweis M. The tuberculosis necrotizing toxin kills macrophages by hydrolyzing NAD. Nat Struct Mol Biol. 2015 Sep;22(9):672-8. doi: 10.1038/nsmb.3064. Epub 2015 Aug , 3. PMID:26237511 doi:http://dx.doi.org/10.1038/nsmb.3064
- ↑ Sun J, Siroy A, Lokareddy RK, Speer A, Doornbos KS, Cingolani G, Niederweis M. The tuberculosis necrotizing toxin kills macrophages by hydrolyzing NAD. Nat Struct Mol Biol. 2015 Sep;22(9):672-8. doi: 10.1038/nsmb.3064. Epub 2015 Aug , 3. PMID:26237511 doi:http://dx.doi.org/10.1038/nsmb.3064
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