Hydrolysis of the phosphoanhydride linkage of cyclic ADP‐ribose by the Mn2+‐dependent ADP‐ribose/CDP‐alcohol pyrophosphatase

• Published in: FEBS letters Vol. 583; no. 10; pp. 1593 - 1598
• Main Authors: Canales, José, Fernández, Ascensión, Rodrigues, Joaquim Rui, Ferreira, Rui, Ribeiro, João Meireles, Cabezas, Alicia, Costas, María Jesús, Cameselle, José Carlos
• Format: Journal Article
• Language: English
• Published: 19.05.2009
• Subjects: ADP-ribose; ADPRibase-Mn; cADPR; cyclic ADP-ribose; dimethylsulfoxide; DMSO; Histidine biosynthesis; Immune signaling; Mn2+-dependent ADP-ribose/CDP-alcohol pyrophosphatase; N 1-(5-phosphoribosyl)-adenosine; N 1-(5-phosphoribosyl)-adenosine 5′-monophosphate; N 1-(5-phosphoribosyl)-adenosine 5′-triphosphate; N 1-(ribosyl)-adenosine; N 1-(ribosyl)-adenosine 5′-monophosphate; NAD glycohydrolase; NADase; Phosphoribosyl-AMP; pRib-Ado; pRib-AMP; pRib-ATP; Pyrophosphatase; Rib-Ado; Rib-AMP
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2009.04.023

Cyclic ADP‐ribose (cADPR) metabolism in mammals is catalyzed by NAD glycohydrolases (NADases) that, besides forming ADP‐ribose, form and hydrolyze the N 1‐glycosidic linkage of cADPR. Thus far, no cADPR phosphohydrolase was known. We tested rat ADP‐ribose/CDP‐alcohol pyrophosphatase (ADPRibase‐Mn) and found that cADPR is an ADPRibase‐Mn ligand and substrate. ADPRibase‐Mn activity on cADPR was 65‐fold less efficient than on ADP‐ribose, the best substrate. This is similar to the ADP‐ribose/cADPR formation ratio by NADases. The product of cADPR phosphohydrolysis by ADPRibase‐Mn was N 1‐(5‐phosphoribosyl)‐AMP, suggesting a novel route for cADPR turnover.