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==Atomic structure of tuberculosis necrotizing toxin (TNT) complexed with its immunity factor IFT==
==Atomic structure of tuberculosis necrotizing toxin (TNT) complexed with its immunity factor IFT==
<StructureSection load='4qlp' size='340' side='right' caption='[[4qlp]], [[Resolution|resolution]] 1.10&Aring;' scene=''>
<StructureSection load='4qlp' size='340' side='right'caption='[[4qlp]], [[Resolution|resolution]] 1.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4qlp]] is a 2 chain structure. 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='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://www.rcsb.org/pdb/explore.do?structureId=4qlp RCSB], [http://www.ebi.ac.uk/pdbsum/4qlp PDBsum]</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]] 1.1&#8491;</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>
</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;">
== 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<ref>PMID:26237511</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4qlp" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Cingolani, G]]
[[Category: Large Structures]]
[[Category: Doornbos, K S]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Lokareddy, R K]]
[[Category: Cingolani G]]
[[Category: Niederweis, M]]
[[Category: Doornbos KS]]
[[Category: Siroy, A]]
[[Category: Lokareddy RK]]
[[Category: Speer, A]]
[[Category: Niederweis M]]
[[Category: Sun, J]]
[[Category: Siroy A]]
[[Category: B-nad+ glycohydrolase]]
[[Category: Speer A]]
[[Category: Duf4237]]
[[Category: Sun J]]
[[Category: Factor rv3902c renamed here as immunity factor of tnt]]
[[Category: Hydrolase-protein binding complex]]
[[Category: Membrane]]
[[Category: Nad-binding domain]]
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