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

Canales, José; Fernández, Ascensión; Rodrigues, Joaquim Rui; Ferreira, Rui; Ribeiro, João Meireles; Cabezas, Alicia; Costas, María Jesús; Cameselle, José Carlos

doi:10.1016/j.febslet.2009.04.023

« Previous Next »FEBS Letters
Volume 583, Issue 10 , Pages 1593-1598, 19 May 2009

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

Edited by Judit Ovádi

José Canales
- Grupo de Enzimología, Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Medicina, Universidad de Extremadura, Apartado 108, E-06080 Badajoz, Spain
Ascensión Fernández
- Grupo de Enzimología, Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Medicina, Universidad de Extremadura, Apartado 108, E-06080 Badajoz, Spain
Joaquim Rui Rodrigues
- Escola Superior de Tecnologia e Gestão, Instituto Politécnico de Leiria, Leiria, Portugal
Rui Ferreira
- Departamento de Química, Universidade de Évora, Évora, Portugal
João Meireles Ribeiro
- Grupo de Enzimología, Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Medicina, Universidad de Extremadura, Apartado 108, E-06080 Badajoz, Spain
Alicia Cabezas
- Grupo de Enzimología, Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Medicina, Universidad de Extremadura, Apartado 108, E-06080 Badajoz, Spain
María Jesús Costas
- Grupo de Enzimología, Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Medicina, Universidad de Extremadura, Apartado 108, E-06080 Badajoz, Spain
José Carlos Cameselle
- Grupo de Enzimología, Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Medicina, Universidad de Extremadura, Apartado 108, E-06080 Badajoz, Spain
- Corresponding author. Fax: +34 924289468.

Received 27 March 2009; accepted 9 April 2009. published online 20 April 2009.

Abstract

Cyclic ADP-ribose (cADPR) metabolism in mammals is catalyzed by NAD glycohydrolases (NADases) that, besides forming ADP-ribose, form and hydrolyze the N¹-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 N¹-(5-phosphoribosyl)-AMP, suggesting a novel route for cADPR turnover.

Abbreviations: ADPRibase-Mn, Mn²⁺-dependent ADP-ribose/CDP-alcohol pyrophosphatase, cADPR, cyclic ADP-ribose, DMSO, dimethylsulfoxide, NADase, NAD glycohydrolase, pRib-Ado, N¹-(5-phosphoribosyl)-adenosine, pRib-AMP, N¹-(5-phosphoribosyl)-adenosine 5′-monophosphate, pRib-ATP, N¹-(5-phosphoribosyl)-adenosine 5′-triphosphate, Rib-Ado, N¹-(ribosyl)-adenosine, Rib-AMP, N¹-(ribosyl)-adenosine 5′-monophosphate