Production of Calcium-Mobilizing Metabolites by a Novel Member of the ADP-Ribosyl Cyclase Family Expressed inSchistosoma mansoni,

• DOI: 10.1021/bi050704r
• Publication Date: 2005-08-16T04:39:52Z
• Authors: Stephen P. Goodrich; Hélène Muller-Ste...; Ahmed Osman; Marie-Jo Moutin; Kim Kusser; Alan Roberts; David L. Woodland; Troy D. Randall; Esther Kellenberger; Philip T. LoVerde; Francis Schuber; Frances E. Lund
• Keywords: Cyclic ADP-Ribose

ADP-ribosyl cyclases are structurally conserved enzymes that best known for catalyzing the production of calcium-mobilizing metabolite, cyclic adenosine diphosphate ribose (cADPR), from nicotinamide adenine dinucleotide (NAD+). However, these also produce (ADPR) and nicotinic acid phosphate (NAADP+), both which have been shown to modulate calcium mobilization in vitro. We now characterized a new member cyclase family Schistosoma mansoni, Platyhelminthes phylum. show novel NAD(P)+ catabolizing enzyme (NACE) expressed by schistosomes is most closely related cloned Aplysia but shows significant homology with mammalian cyclases, CD38 CD157. NACE expression developmentally regulated schistosomes, GPI-anchored protein localized outer tegument adult schistosome. Importantly, NACE, like all members family, multifunctional catalyzes NAD+ glycohydrolase base-exchange reactions ADPR NAADP+. despite being competent generate product NGD+, nonphysiologic surrogate substrate, so far only unable amounts cADPR (<0.02% reaction products) using as substrate. This suggests other metabolites produced may be more important signaling schistosomes. Alternatively, function catabolize extracellular prevent its use host utilize this source facilitate immune responses.