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Cyclic ADP-ribose

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Cyclic ADP-ribose
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.162.252Edit this at Wikidata
MeSH Cyclic+ADP-Ribose
UNII
  • InChI=1S/C15H21N5O13P2/c16-12-7-13-18-4-19(12)14-10(23)8(21)5(31-14)1-29-34(25,26)33-35(27,28)30-2-6-9(22)11(24)15(32-6)20(13)3-17-7/h3-6,8-11,14-16,21-24H,1-2H2,(H,25,26)(H,27,28)/t5-,6-,8-,9-,10-,11-,14-,15-/m1/s1☒N
    Key: BQOHYSXSASDCEA-KEOHHSTQSA-N☒N
  • InChI=1/C15H21N5O13P2/c16-12-7-13-18-4-19(12)14-10(23)8(21)5(31-14)1-29-34(25,26)33-35(27,28)30-2-6-9(22)11(24)15(32-6)20(13)3-17-7/h3-6,8-11,14-16,21-24H,1-2H2,(H,25,26)(H,27,28)/t5-,6-,8-,9-,10-,11-,14-,15-/m1/s1
    Key: BQOHYSXSASDCEA-KEOHHSTQBN
  • O[C@H]5[C@@H](O)[C@H]2O[C@@H]5COP(O)(=O)OP(O)(=O)OC[C@H]4O[C@@H](N3\C=N/c1c(ncn12)C3=N)[C@H](O)[C@@H]4O
Properties
C15H21N5O13P2
Molar mass 541.301
Except where otherwise noted, data are given for materials in theirstandard state(at 25 °C [77 °F], 100 kPa).

Cyclic ADP-ribose,frequently abbreviated ascADPR,is a cyclic adenine nucleotide (likecAMP) with two phosphate groups present on 5' OH of theadenosine(likeADP), further connected to anotherriboseat the 5' position, which, in turn, closes the cycle byglycosidic bondingto the nitrogen 1 (N1) of the sameadeninebase (whose position N9has the glycosidic bond to the otherribose).[1][2]The N1-glycosidic bond to adenine is what distinguishes cADPR fromADP-ribose(ADPR), the non-cyclic analog. cADPR is produced fromnicotinamide adenine dinucleotide(NAD+) by ADP-ribosyl cyclases (EC 3.2.2.5) as part of asecond messenger system.

Function[edit]

cADPR is a cellular messenger forcalcium signaling.[3]It stimulates calcium-induced calcium release at lower cytosolic concentrations of Ca2+.The primary target of cADPR is theendoplasmic reticulumCa2+uptake mechanism. cADPR mobilizes Ca2+from the endoplasmic reticulum by activation ofryanodine receptors,[4]a critical step in muscle contraction.[5]

cADPR also acts as anagonistfor theTRPM2channel, but less potently thanADPR.[6]cADPR and ADPR actsynergistically,with both molecules enhancing the action of the other molecule in activating the TRPM2 channel.[7]

Potentiation of Ca2+release by cADPR is mediated by increased accumulation of Ca2+in thesarcoplasmic reticulum.[8]

Metabolism[edit]

cADPR and ADPR are synthesized from NAD+by the bifunctional ectoenzymes of theCD38family (also includes theGPI-anchoredCD157and the specific, monofunctional ADP ribosyl cyclase of the molluscAplysia).[9][10][11]The same enzymes are also capable of hydrolyzing cADPR toADPR.Catalysis proceeds via a covalently bound intermediate. The hydrolysis reaction is inhibited byATP,and cADPR may accumulate. Synthesis and degradation of cADPR by enzymes of the CD38 family involve, respectively, the formation and the hydrolysis of the N1-glycosidic bond. In 2009, the first enzyme able to hydrolyze the phosphoanhydride linkage of cADPR, i.e. the one between the two phosphate groups, was reported.[12]

SARM1and otherTIR domain-containing proteins also catalyze the formation of cADPR from NAD+.[13][14]

Isomers[edit]

Variants of cADPR that differ in theirHPLCretention times compared to canonical cADPR have been identified as products of bacterial and plantTIR domain-containing enzymes.[14][15]v-cADPR (also referred to as 2'cADPR or 1''-2' glycocyclic ADPR (gcADPR)) and v2-cADPR (also referred to as 3'cADPR or 1''-3' gcADPR) isomers are cyclized by O-glycosidic bond formation between the ribose moieties in ADPR.[16][17]3'cADPR produced by bacterialTIR domain-containing proteins can act as an activator of bacterial antiphage defense systems and as a suppressor of plant immunity.[16]

See also[edit]

References[edit]

  1. ^Lee HC, Walseth TF, Bratt GT, Hayes RN, Clapper DL (1989)."Structural determination of a cyclic metabolite of NAD+with intracellular Ca2+-mobilizing activity ".J. Biol. Chem.264(3): 1608–15.doi:10.1016/S0021-9258(18)94230-4.PMID2912976.
  2. ^Lee HC, Aarhus R, Levitt D (1994). "The crystal structure of cyclic ADP-ribose".Nat. Struct. Biol.1(3): 143–4.doi:10.1038/nsb0394-143.PMID7656029.S2CID9049850.
  3. ^Guse AH (2004). "Regulation of calcium signaling by the second messenger cyclic adenosine diphosphoribose (cADPR)".Curr. Mol. Med.4(3): 239–48.doi:10.2174/1566524043360771.PMID15101682.
  4. ^Galione A, Chuang K (2020). "Pyridine Nucleotide Metabolites and Calcium Release from Intracellular Stores".Calcium Signaling.Advances in Experimental Medicine and Biology. Vol. 1131. pp. 371–394.doi:10.1007/978-3-030-12457-1_15.ISBN978-3-030-12456-4.PMID31646518.S2CID204865377.
  5. ^Santulli G, Marks AR (2015). "Essential Roles of Intracellular Calcium Release Channels in Muscle, Brain, Metabolism, and Aging".Current Molecular Pharmacology.8(2): 206–22.doi:10.2174/1874467208666150507105105.PMID25966694.
  6. ^Yu P, Cai X, Liang Y, Yang W (2019)."Roles of NAD + and Its Metabolites Regulated Calcium Channels in Cancer".Molecules.25(20): 4826.doi:10.3390/molecules25204826.PMC7587972.PMID33092205.
  7. ^Lee HC (2011)."Cyclic ADP-ribose and NAADP: fraternal twin messengers for calcium signaling".Science China Life Sciences.54(8): 699–711.doi:10.1007/s11427-011-4197-3.PMID21786193.S2CID24286381.
  8. ^Lukyanenko, V; Györke, I; Wiesner, T. F.; Györke, S (2001)."Potentiation of Ca(2+) release by cADP-ribose in the heart is mediated by enhanced SR Ca(2+) uptake into the sarcoplasmic reticulum".Circulation Research.89(7): 614–22.doi:10.1161/hh1901.098066.PMID11577027.
  9. ^Prasad GS, McRee DE, Stura EA, Levitt DG, Lee HC, Stout CD (1996). "Crystal structure of Aplysia ADP-ribosyl cyclase, a homolog of the bifunctional ectozyme CD38".Nat. Struct. Biol.3(11): 957–64.doi:10.1038/nsb1196-957.PMID8901875.S2CID21978229.
  10. ^Liu Q, Kriksunov IA, Graeff R, Munshi C, Lee HC, Hao Q (2005)."Crystal structure of the human CD38 extracellular domain".Structure.13(9): 1331–9.doi:10.1016/j.str.2005.05.012.PMID16154090.
  11. ^Guse AH (2004). "Biochemistry, biology, and pharmacology of cyclic adenosine diphosphoribose (cADPR)".Curr. Med. Chem.11(7): 847–55.doi:10.2174/0929867043455602.PMID15078169.
  12. ^Canales J, Fernández A, Rodrigues JR, Ferreira R, Ribeiro JM, Cabezas A, Costas MJ, Cameselle JC (2009). "Hydrolysis of the phosphoanhydride linkage of cyclic ADP-ribose by the Mn2+-dependent ADP-ribose/CDP-alcohol pyrophosphatase ".FEBS Lett.583(10): 1593–8.doi:10.1016/j.febslet.2009.04.023.hdl:10400.8/3028.PMID19379742.S2CID28571921.
  13. ^Lee HC, Zhao YJ (2019)."Resolving the topological enigma in Ca 2+ signaling by cyclic ADP-ribose and NAADP".Journal of Biological Chemistry.294(52): 19831–19843.doi:10.1074/jbc.REV119.009635.PMC6937575.PMID31672920.
  14. ^abEssuman, Kow; Summers, Daniel W.; Sasaki, Yo; Mao, Xianrong; Yim, Aldrin Kay Yuen; DiAntonio, Aaron; Milbrandt, Jeffrey (2018-02-05)."TIR Domain Proteins Are an Ancient Family of NAD+-Consuming Enzymes".Current Biology.28(3): 421–430.e4.doi:10.1016/j.cub.2017.12.024.ISSN1879-0445.PMC5802418.PMID29395922.
  15. ^Wan, Li; Essuman, Kow; Anderson, Ryan G.; Sasaki, Yo; Monteiro, Freddy; Chung, Eui-Hwan; Osborne Nishimura, Erin; DiAntonio, Aaron; Milbrandt, Jeffrey; Dangl, Jeffery L.; Nishimura, Marc T. (2019-08-23)."TIR domains of plant immune receptors are NAD+-cleaving enzymes that promote cell death".Science.365(6455): 799–803.doi:10.1126/science.aax1771.ISSN1095-9203.PMC7045805.PMID31439793.
  16. ^abManik, Mohammad K.; Shi, Yun; Li, Sulin; Zaydman, Mark A.; Damaraju, Neha; Eastman, Samuel; Smith, Thomas G.; Gu, Weixi; Masic, Veronika; Mosaiab, Tamim; Weagley, James S.; Hancock, Steven J.; Vasquez, Eduardo; Hartley-Tassell, Lauren; Kargios, Nestoras (2022-09-30)."Cyclic ADP ribose isomers: Production, chemical structures, and immune signaling".Science.377(6614): eadc8969.doi:10.1126/science.adc8969.ISSN1095-9203.PMID36048923.S2CID252010170.
  17. ^Leavitt, Azita; Yirmiya, Erez; Amitai, Gil; Lu, Allen; Garb, Jeremy; Herbst, Ehud; Morehouse, Benjamin R.; Hobbs, Samuel J.; Antine, Sadie P.; Sun, Zhen-Yu J.; Kranzusch, Philip J.; Sorek, Rotem (2022-09-29)."Viruses inhibit TIR gcADPR signaling to overcome bacterial defense".Nature.611(7935): 326–331.doi:10.1038/s41586-022-05375-9.ISSN1476-4687.PMID36174646.S2CID248529724.

External links[edit]

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