Reaction: NAD+ = (1''-2')-cyclic adenosine diphosphate-β-D-ribose + nicotinamide
Glossary: (1''-2')-cyclic adenosine diphosphate-β-D-ribose = 1,2'-anhydroadenine(5')diphosphate(5)-β-D-ribose = 1''-2' glycocyclic ADP-β-D-ribose = (1''-2')-cyclic ADP-β-D-ribose = 2'-cADPR = 1''-2' gcADPR = v-cADPR
Other name(s): 2'cADPR synthase; AbTIR; L6 (gene name); ROQ1 (gene name)
Systematic name: NAD+ lyase [(1''-2')-cyclic adenosine diphosphate-β-D-ribose-forming]
Comments: The enzyme, found in plants and bacteria, contains a TIR (Toll/interleukin-1 receptor) domain. Activity requires self-association into larger aggregates. In plants (1''-2')-cyclic adenosine diphosphate-β-D-ribose triggers localized cell death in response to infections [1-3]. The bacterial enzyme was shown to form filamentous structures, with substrate molecules present between the monomers [4]. cf. EC 4.3.99.7, 3'-cyclic-ADP-D-ribose synthase, and EC 3.2.2.6, ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Horsefield, S., Burdett, H., Zhang, X., Manik, M.K., Shi, Y., Chen, J., Qi, T., Gilley, J., Lai, J.S., Rank, M.X., Casey, L.W., Gu, W., Ericsson, D.J., Foley, G., Hughes, R.O., Bosanac, T., von Itzstein, M., Rathjen, J.P., Nanson, J.D., Boden, M., Dry, I.B., Williams, S.J., Staskawicz, B.J., Coleman, M.P., Ve, T., Dodds, P.N. and Kobe, B. NAD(+) cleavage activity by animal and plant TIR domains in cell death pathways. Science 365 (2019) 793-799. [PMID: 31439792]
2. Wan, L., Essuman, K., Anderson, R.G., Sasaki, Y., Monteiro, F., Chung, E.H., Osborne Nishimura, E., DiAntonio, A., Milbrandt, J., Dangl, J.L. and Nishimura, M.T. TIR domains of plant immune receptors are NAD(+)-cleaving enzymes that promote cell death. Science 365 (2019) 799-803. [PMID: 31439793]
3. Duxbury, Z., Wang, S., MacKenzie, C.I., Tenthorey, J.L., Zhang, X., Huh, S.U., Hu, L., Hill, L., Ngou, P.M., Ding, P., Chen, J., Ma, Y., Guo, H., Castel, B., Moschou, P.N., Bernoux, M., Dodds, P.N., Vance, R.E. and Jones, J.DG. Induced proximity of a TIR signaling domain on a plant-mammalian NLR chimera activates defense in plants. Proc. Natl. Acad. Sci. USA 117 (2020) 18832-18839. [PMID: 32709746]
4. Manik, M.K., Shi, Y., Li, S., Zaydman, M.A., Damaraju, N., Eastman, S., Smith, T.G., Gu, W., Masic, V., Mosaiab, T., Weagley, J.S., Hancock, S.J., Vasquez, E., Hartley-Tassell, L., Kargios, N., Maruta, N., Lim, B.YJ., Burdett, H., Landsberg, M.J., Schembri, M.A., Prokes, I., Song, L., Grant, M., DiAntonio, A., Nanson, J.D., Guo, M., Milbrandt, J., Ve, T. and Kobe, B. Cyclic ADP ribose isomers: Production, chemical structures, and immune signaling. Science 377 (2022) eadc8969. [PMID: 36048923]