Reaction participants Show >> << Hide
- Name help_outline NAD+ Identifier CHEBI:57540 (Beilstein: 3868403) help_outline Charge -1 Formula C21H26N7O14P2 InChIKeyhelp_outline BAWFJGJZGIEFAR-NNYOXOHSSA-M SMILEShelp_outline NC(=O)c1ccc[n+](c1)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)n2cnc3c(N)ncnc23)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,142 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline phosphate Identifier CHEBI:43474 Charge -2 Formula HO4P InChIKeyhelp_outline NBIIXXVUZAFLBC-UHFFFAOYSA-L SMILEShelp_outline OP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 983 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline ADP-α-D-ribose 1''-phosphate Identifier CHEBI:58753 Charge -4 Formula C15H20N5O17P3 InChIKeyhelp_outline CUNFRFHBHMFVPH-KEOHHSTQSA-J SMILEShelp_outline Nc1ncnc2n(cnc12)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H](OP([O-])([O-])=O)[C@H](O)[C@@H]2O)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 3 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,176 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline nicotinamide Identifier CHEBI:17154 (Beilstein: 383619; CAS: 98-92-0) help_outline Charge 0 Formula C6H6N2O InChIKeyhelp_outline DFPAKSUCGFBDDF-UHFFFAOYSA-N SMILEShelp_outline NC(=O)c1cccnc1 2D coordinates Mol file for the small molecule Search links Involved in 60 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:20788 | RHEA:20789 | RHEA:20790 | RHEA:20791 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Publications
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An NAD+ phosphorylase toxin triggers Mycobacterium tuberculosis cell death.
Freire D.M., Gutierrez C., Garza-Garcia A., Grabowska A.D., Sala A.J., Ariyachaokun K., Panikova T., Beckham K.S.H., Colom A., Pogenberg V., Cianci M., Tuukkanen A., Boudehen Y.M., Peixoto A., Botella L., Svergun D.I., Schnappinger D., Schneider T.R., Genevaux P., de Carvalho L.P.S., Wilmanns M., Parret A.H.A., Neyrolles O.
Toxin-antitoxin (TA) systems regulate fundamental cellular processes in bacteria and represent potential therapeutic targets. We report a new RES-Xre TA system in multiple human pathogens, including Mycobacterium tuberculosis. The toxin, MbcT, is bactericidal unless neutralized by its antitoxin Mb ... >> More
Toxin-antitoxin (TA) systems regulate fundamental cellular processes in bacteria and represent potential therapeutic targets. We report a new RES-Xre TA system in multiple human pathogens, including Mycobacterium tuberculosis. The toxin, MbcT, is bactericidal unless neutralized by its antitoxin MbcA. To investigate the mechanism, we solved the 1.8 Å-resolution crystal structure of the MbcTA complex. We found that MbcT resembles secreted NAD<sup>+</sup>-dependent bacterial exotoxins, such as diphtheria toxin. Indeed, MbcT catalyzes NAD<sup>+</sup> degradation in vitro and in vivo. Unexpectedly, the reaction is stimulated by inorganic phosphate, and our data reveal that MbcT is a NAD<sup>+</sup> phosphorylase. In the absence of MbcA, MbcT triggers rapid M. tuberculosis cell death, which reduces mycobacterial survival in macrophages and prolongs the survival of infected mice. Our study expands the molecular activities employed by bacterial TA modules and uncovers a new class of enzymes that could be exploited to treat tuberculosis and other infectious diseases. << Less