The ARH and Macrodomain Families of α-ADP-ribose-acceptor Hydrolases Catalyze α-NAD^<b>+</b> Hydrolysis.

ABSTRACT: ADP-ribosyltransferases transfer ADP-ribose from β-NAD⁺ to acceptors; ADP-ribosylated acceptors are cleaved by ADP-ribosyl-acceptor hydrolases (ARHs) and proteins containing ADP-ribose-binding modules termed macrodomains. On the basis of the ADP-ribosyl-arginine hydrolase 1 (ARH1) stereospecific hydrolysis of α-ADP-ribosyl-arginine and the hypothesis that α-NAD⁺ is generated as a side product of β-NAD⁺/ NADH metabolism, we proposed that α-NAD⁺ was a substrate of ARHs and macrodomain proteins. Here, we report that ARH1, ARH3, and macrodomain proteins (i.e., MacroD1, MacroD2, C6orf130 (TARG1), Af1521, hydrolyzed α-NAD⁺ but not β-NAD⁺. ARH3 had the highest α-NADase specific activity. The ARH and macrodomain protein families, in

SUBMITTER: Stevens LA 

PROVIDER: S-EPMC8388552 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature