3.2.2.6 cyclic ADP-ribose + H2O = ADP-D-ribose (1b) - 3.2.2.6 NAD+ + H2O = ADP-D-ribose + nicotinamide + H+ (overall reaction) - 3.2.2.6 NAD+ + H2O = ADP-D-ribose + nicotinamide + H+ also catalyses transfer of ADP-ribose(P) residues 326409 3.2.2.6 NAD+ + H2O = ADP-D-ribose + nicotinamide + H+ reaction mechanism, overview 731119 3.2.2.6 NAD+ + H2O = ADP-D-ribose + nicotinamide + H+ structure-function analysis and reaction mechanism, overview. The nicotinamide-ribosyl bond of NAD+ is cleaved via a dissociative process with a late transition state, leading to a ribooxocarbenium ion reaction intermediate stabilized by the side-chain of invariant Glu218. This rate-determining step is followed by two nucleophilic reactions in competition: (i) an intermolecular pathway involving a rapid trapping from the b-face of this intermediate by a water molecule (NAD+ glycohydrolase activity) or by competing neutral nucleophiles such as pyridines (transglycosidation reactions) or alcohols (e.g., methanolysis), and (ii) an intramolecular reaction between N1 of the adenine ring and C19 (anomeric carbon) of the oxocarbenium ion leading to the formation of cyclic ADP-ribose (ADP-ribosyl cyclase activity). This latter reaction represents a kinetically minor step relative to solvolysis 732691 3.2.2.6 NAD+ + H2O = ADP-D-ribose + nicotinamide + H+ substrate binding with a crucial role of Glu218, which orients the substrate for cleavage by interacting with the N-ribosyl 2'-OH group of NAD+, stepwise ordered uni-bi kinetic mechanism, overview. Residues Trp118, Glu138, Asp147, Trp181 stabilize the ribooxocarbenium ion-like transition state mostly by electrostatic interactions 731357 3.2.2.6 NAD+ = cyclic ADP-ribose + nicotinamide (1a) -